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>>WELCOME TO THE 13TH
SESSION

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OF THE 23RD YEAR OF A COURSE

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CALLED DEMYSTIFYING MEDICINE,

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HELD AT THE NATIONAL INSTITUTES

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OF HEALTH IN BETHESDA, MARYLAND.

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I'M WIN ARIAS, A SENIOR

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SCIENTIST EMERITUS, AND ONE OF

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YOUR HOSTS FOR THIS PROGRAM.

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THE OTHER IS DAN KASTNER OF THE

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HUMAN GENOME RESEARCH INSTITUTE.

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AND WE WELCOME YOU ALL TO THIS

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AFTERNOON'S SESSION ON A TOPIC

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OF ENORMOUS INTEREST,

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IMPORTANCE, EXCITEMENT, AND

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ACTUALLY IS OF GREAT INTEREST TO

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EVERYONE.

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THE PURPOSE OF THIS COURSE IS TO

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ACT LIKE A BRIDGE TO BRIDGE

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EXCITING DEVELOPMENTS IN BIOLOGY

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AND ENGINEERING WITH CLINICAL

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MEDICINE.

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THE LOGO IN THE UPPER RIGHT-HAND

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CORNER ON MY SCREEN IS THE

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BROOKLYN BRIDGE.

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AND TWO FOLKS ON THE CATWALK

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REPRESENT TODAY'S SPEAKERS, WHO

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ARE DISCUSSING THE IMPORTANT

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PROBLEM OF OBESITY FROM TWO VERY

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DIFFERENT PERSPECTIVES.

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AND THE PURPOSE OF A BRIDGE IS

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TO SHARE NEW IDEAS WITH THOSE

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WHO ARE NOT IMMEDIATELY AWARE OF

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THEM.

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MUCH OF OUR SCIENCE TODAY IS IN

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THE FORM OF A SILO SHOWN IN THE

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LOWER RIGHT-HAND SECTION.

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WHERE WE ALL KNOW AS IF IT WERE

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SMALL PIECES OF THE PIZZA PIE,

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BUT WE DO NOT COMMUNICATE

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BROADLY ACROSS EITHER BIOLOGY OR

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ENGINEERING OR CLINICAL MEDIC 

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MEDICINE.

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SO IN THIS COURSE, WE TRY TO

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CREATE MANY DIFFERENT KINDS OF

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BRIDGES, AND FREQUENTLY START

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WITH A LIVE PATIENT WHO

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DESCRIBES THEIR DISEASE IN THEIR

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OWN WORDS, AND THEN A CLINICIAN

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AND INVESTIGATOR, AND FINALLY A

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BASIC SCIENTIST WHO DESCRIBES

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WHAT DO WE KNOW AND WHAT DO WE

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REALLY NEED TO KNOW AND WHAT IS

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THE CHALLENGE FOR YOUNG PEOPLE

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LIKE YOU WHO ARE WATCHING THIS

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PROGRAM AROUND THE WORLD.

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THIS VIRTUAL SCHEDULE HAS

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EXPANDED THE SCOPE OF

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DEMYSTIFYING MEDICINE, WHICH IS

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NOW WATCHED IN OVER 

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38 COUNTRIES AROUND

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THE WORLD.

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IN THE 17TH, 18TH AND EARLY

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19TH CENTURY, OBESITY WAS A SIGN

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OF, AS ONE OF THE SPEAKERS JUST

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INFORMED ME, PROBABLY OF WEALTH,

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AND IT CERTAINLY WAS ENVIABLE.

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MEN HAD BIG BELLIES, EVEN

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NAPOLEON HAD A RATHER HUGE

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ABDOMEN, ABDOMINAL BIG BELLY.

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AND THEN THINGS CHANGED.

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MAYBE BECAUSE THE IMAGES CHAN

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CHANGED, FROM HISTORICAL

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FIGURES, TELEVISION, MOVIES,

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BROUGHT OUT THE IDEA THAT THE

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HEROS WERE SLIM MEN, THINK CARY

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GRANT, AND THE WOMEN LIKEWISE.

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BUT THEN IT CHANGED AGAIN.

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AND IT CREATED WHAT IS A TRUE

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EPIDEMIC.

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OBESITY HAS WORSENED ENORMOUSLY

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IN THE PAST 50 YEARS.

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THE ECONOMIC BURDEN IS ESTIMATED

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TO BE SOMETHING LIKE

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$100 BILLION A YEAR.

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AND IT'S THE SECOND MOST COMMON

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CAUSE OF PREVENTABLE DEATH,

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SMOKING BEING THE FIRST.

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NOW, IN OUR COUNTRY, EVEN 40, 50

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YEARS AGO, THE STATEMENT AT THE

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TOP OF THIS SLIDE PRETTY MUCH

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TOLD THE STORY.

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FAT WAS FAT, AND THAT WAS THAT.

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BUT MY, HOW THINGS HAVE CHANGED.

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WE NOW RECOGNIZE THAT ADIPOSE

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TISSUE IS DIVERSE.

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THERE'S WHITE FAT AND BROWN FAT.

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THEY'RE METABOLICALLY AND

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HORMONALLY DIFFERENT.

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AND ALL FAT IS METABOLICALLY AND

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HORMONALLY AN ACTIVE TISSUE.

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IT RELEASES FREE FATTY ACIDS,

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PRODUCES HORMONES OF DIFFERENT

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KINDS, WHICH ACT ON BRAIN,

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LIVER, MUSCLE AND OTHER TISSUES

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TO REGULATE FOOD INTAKE, ENERGY

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BALANCE, AND INSULIN

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SENSITIVITY.

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AS A RESULT OF THESE

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MANIFESTATIONS, OTHER EFFECTS

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INVOLVED INFLAMMATION, IMMUNITY

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AND PREDISPOSITION TO CANCER,

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DIABETES, CARDIOVASCULAR, AND

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NEURODEGENERATIVE DISEASES.

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AND PROBABLY OTHERS.

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NOW, TO BALANCE THIS EXPLOSION

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OF SCIENTIFIC INFORMATION

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REGARDING WHAT FAT IS AND WHAT

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IT DOES, THERE IS A HUGE

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CLINICAL CHALLENGE TO RELATE THE

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DISCOVERIES BEING MADE TO

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ADVANCES IN NUTRITION, HEALTH,

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AND WHETHER PROPOSED TREATMENTS,

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PARTICULARLY THOSE POPULAR WITH

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A LARGE NUMBER OF PEOPLE,

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WHETHER THOSE TREATMENTS,

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DIETARY OR PHARMACOLOGIC WORK,

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AND IF SO, HOW DO THEY WORK?

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NOW, THIS IS THE BALLPARK OF

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TODAY'S DEMYSTIFYING MEDICINE.

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AND WE ARE VERY PLEASED TO HAVE

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TWO NIH LEADERS IN THIS FIELD.

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NOW OUR FIRST SPEAKER IS GOING

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TO BE AARON CYPESS.

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AARON WAS A GRADUATE OF

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PRINCETON, TOOK A PH.D. FROM

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ROCKEFELLER UNIVERSITY, AND HIS

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MEDICAL DEGREE FROM CORNEL, AND

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THEN A MASTER OF MEDICAL

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SCIENCES AT HARVARD.

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HE DID A RESIDENCY AT BETH

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ISRAEL DEACONESS MEDICAL CENTER

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IN BOSTON AND BECAME AN

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ASSISTANT INVESTIGATOR, STAFF

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PHYSICIAN AT THE JOSLIN DIABETES

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CENTER AND THEN ASSISTANT

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PROFESSOR OF MEDICINE AT HARVARD

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MEDICAL SCHOOL UNTIL 2014.

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WHEN HE WAS RECRUITED TO THE

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NATIONAL INSTITUTES OF DIABETES,

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DIGESTIVE DISEASE AND KIDNEY AS

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THE ACTING CHIEF OF THE

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TRANSLATIONAL PHYSIOLOGY SECTION

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IN THE DIABETES, ENDOCRINE AND

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OBESITY BRANCH OF NIDDK.

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SO AARON RESEARCHES WHITE AND

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BROWN FA FAT STRUCTURE, PHYSIOL,

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RELATION TO METABOLIC DISEASE,

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AND SEEKS TO DEVELOP

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PHARMACOLOGIC TREATMENT OF

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OBESITY-RELATED METABOLIC

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DISEASES, AND IN THIS PROCESS,

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HE ALSO USES EXTENSIVELY

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CLINICAL TRIALS BASED TO A GREAT

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EXTENT IN THE CLINICAL CENTER AT

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THE NIH.

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HIS APPROACH IS ONE OF

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INTEGRATIVE PHYSIOLOGY, USING IN

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VITRO AND IN VIVO MODELS AS WELL

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AS CLINICAL TRIALS, AND THEY'VE

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DEVELOPED NONINVASIVE IMAGING

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TECHNIQUES FOR THE

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QUANTIFICATION OF BROWN FAT MASS

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AND ACTIVITY.

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AND HAVE DEVELOPED THERAPEUTIC

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ATTEMPTS TO INCREASE BROWN FAT

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METABOLIC ACTIVITY AND CLINICAL

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USE.

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OUR SECOND SPEAKER, NEXT SLIDE,

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PLEASE, IS KEVIN HALL.

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SO KEVIN IS A PHYSICIST, AND HE

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HAS APPLIED A PHYSICIST'S VIEW

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TO THE UNDERSTANDING OF ENERGY

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EXPENDITURE AND EXPERIMENTAL

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MODELS, IN MATHEMATICAL MODELS,

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AND IN STUDIES, EXTENSIVE

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STUDIES, IN HUMAN PATIENTS.

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HE RECEIVED A PH.D. IN PHYSICS

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FROM MCGILL UNIVERSITY, AND FROM

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2003 TO THE PRESENT TIME, IS A

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SENIOR INVESTIGATOR IN THE

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INTEGRATIVE PHYSIOLOGY SECTION

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IN THE LABORATORY OF BIOLOGICAL

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MODELING AT THE NATIONAL

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INSTITUTE OF DIABETES, DIGESTIVE

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DISEASE AND KIDNEY.

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KEVIN HEADS A TEAM OF

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MATHEMATICIANS, NEUROSCIENTISTS,

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DIETITIANS AND CLINICIANS, WHO

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STUDY AND MODEL ENERGY

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EXPENDITURE AND BODY COMPOSITION

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WHEN DIETS AND PHYSICAL ACTIVITY

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ARE ALTERED.

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THE RESULTS HAVE SHAKEN SOME

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LONG-HELD BELIEFS, AND WE WILL

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HEAR MORE ABOUT THIS.

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KEVIN HAS ALSO DEVELOPED A MODEL

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WHICH HAS BEEN USED BY MILLIONS

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OF PEOPLE FOR PREDICTING

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LIFESTYLE CHANGES THAT ARE

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NEEDED IN ORDER TO REACH AND

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MAINTAIN A WEIGHT GOAL.%

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SO IN THESE STUDIES, THEY'VE

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USED FUNCTIONAL MRI, MEASURED

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BRAIN LOCALIZATION AND ACTIVITY

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IN RELATION TO SEEING OR

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INGESTING VARIOUS FOODS.

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THE APPLICATION OF A PHYSICIST'S

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APPROACH TO THE STUDY OF ENERGY

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EXPENDITURE HAS LED TO RESULTS

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THAT WERE COMPLETELY

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UNANTICIPATED.

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AND WHICH HE WILL SHARE WITH US

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TODAY.

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SO OUR FIRST SPEAKER NOW IS

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AARON CYPESS, AND AARON, WILL

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YOU PLEASE TAKE THE BATON.

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>>THANK YOU, DR. ARIAS,
FOR

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THAT DETAILED AND OUTSTANDING

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INTRODUCTION TO OUR WORK.

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I WANT TO THANK YOU AND

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DR. KASTNER AND THE ENTIRE TEAM,

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INCLUDING KENNY AND JOY, FOR

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INVITING ME HERE AND MAKING IT

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POSSIBLE FOR US TO TALK ABOUT

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OUR RESEARCH.

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FAT BIOLOGY AND STAYING THIN IS

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SOMETHING I'VE BEEN THINKING

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ABOUT FOR OVER THREE DECADES IN

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MY PROFESSIONAL CAREER, AND I'M

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GOING TO FOCUS TODAY ON THE

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POLYCHROMATIC HUMAN ADIPOSE

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TISSUE, STRUCTURE AND

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DYSFUNCTION.

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AS MY DISCLOSURE, I WILL BE BE

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DESCRIBING THE USE OF A

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MEDICATION MIRABEGRON,  ABOVE TE

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FDA'S APPROVED DOSE FOR

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OVERACTIVE BL BLADDER.

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THE OBJECTIVES TODAY, FIRST I'D

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LIKE TO IDENTIFY THE MULTIPLE

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TYPES AND SITES OF HUMAN ADIPOSE

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TISSUE.

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THEN WE'LL SUMMARIZE THE CURRENT

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KNOWN PHYSIOLOGICAL ROLES OF

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WHITE AND BROWN ADIPOSE TISSUE,

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OR WAT AND BAT, OR WHITE FAT AND

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BROWN FAT.

258
00:11:47,400 --> 00:11:48,120
THEN WE'LL EXPLAIN THE

259
00:11:48,120 --> 00:11:48,800
CONNECTIONS BETWEEN THE BRAIN

260
00:11:48,800 --> 00:11:50,360
AND FAT IN LEADING TO OBESITY

261
00:11:50,360 --> 00:11:51,800
AND ITS COMPLICATIONS.

262
00:11:51,800 --> 00:11:53,280
AND THEN BY THE END, HOPEFULLY

263
00:11:53,280 --> 00:11:54,960
DEVELOP A HYPOTHESIS AS TO HOW

264
00:11:54,960 --> 00:11:59,400
CHRONIC TREATMENT WITH BETA

265
00:11:59,400 --> 00:12:00,560
3 ADRENERGIC RECEPTOR AGONISTS

266
00:12:00,560 --> 00:12:03,520
WILL IMPACT GLUCOSE AND

267
00:12:03,520 --> 00:12:04,000
LIPOPROTEIN HOMEOSTASIS.

268
00:12:04,000 --> 00:12:06,760
SO I'LL BEGIN WITH A SLIDE THAT

269
00:12:06,760 --> 00:12:07,440
DR. ARIAS REFERRED TO, THAT

270
00:12:07,440 --> 00:12:08,880
THERE IS AN INCREASE IN THE

271
00:12:08,880 --> 00:12:12,040
RATES OF OBESITY AND DIABETES IN

272
00:12:12,040 --> 00:12:12,920
OUR COUNTRY, IT'S A SLIDE MANY

273
00:12:12,920 --> 00:12:14,280
OF YOU HAVE PROBABLY SEEN

274
00:12:14,280 --> 00:12:15,000
BEFORE, AND THE FACT THAT

275
00:12:15,000 --> 00:12:19,040
THEY'RE MOVING IN PARALLEL

276
00:12:19,040 --> 00:12:19,880
INDICATES THAT POSSIBLY TOO MUCH

277
00:12:19,880 --> 00:12:23,720
FAT IS UNHEALTHY.

278
00:12:23,720 --> 00:12:27,400
THABUT IS TOO MUCH FAT UNHEALTH?

279
00:12:27,400 --> 00:12:28,440
IT'S NOT REALLY THAT SIMPLE.

280
00:12:28,440 --> 00:12:29,560
IT'S TIME TO RE-ASSESS.

281
00:12:29,560 --> 00:12:30,880
SO I'M GOING TO START THE TALK

282
00:12:30,880 --> 00:12:31,680
BY GOING THROUGH SOME OF THE

283
00:12:31,680 --> 00:12:33,280
MATERIAL THAT I WROTE ABOUT IN A

284
00:12:33,280 --> 00:12:34,240
REVIEW ARTICLE IN THE NEW

285
00:12:34,240 --> 00:12:35,280
ENGLAND JOURNAL OF MEDICINE

286
00:12:35,280 --> 00:12:36,560
PUBLISHED LAST YEAR, AND IT'S

287
00:12:36,560 --> 00:12:40,920
AVAILABLE FREE ONLINE.

288
00:12:40,920 --> 00:12:42,960
NOW HUMAN WHITE AND BROWN FAT

289
00:12:42,960 --> 00:12:44,440
ARE FOUND THROUGHOUT THE BODY

290
00:12:44,440 --> 00:12:46,160
BUT LOOKS CAN BE DECEIVING SO

291
00:12:46,160 --> 00:12:46,960
WE'LL START WITH THE STRUCTURE.

292
00:12:46,960 --> 00:12:48,720
SO HERE IS THE FRONTAL VIEW OF A

293
00:12:48,720 --> 00:12:49,120
HUMAN.

294
00:12:49,120 --> 00:12:51,000
YOU CAN SEE HERE IN ORANGE IS

295
00:12:51,000 --> 00:12:52,000
THE SUBCUTANEOUS FAT, DIFFERENT

296
00:12:52,000 --> 00:12:53,840
REGIONS ARE INDICATED HERE, AND

297
00:12:53,840 --> 00:12:57,760
THE HEAD, THE DRA CRANIAL REGIO,

298
00:12:57,760 --> 00:13:02,080
THE LIMB, AND THE GLUTEOFEMORAL

299
00:13:02,080 --> 00:13:02,560
RENAL.

300
00:13:02,560 --> 00:13:06,960
THERE ARE BROWN FAT AS WELL,

301
00:13:06,960 --> 00:13:12,920
BROWN AND BEIGE ADIPOCYTES, THE

302
00:13:12,920 --> 00:13:15,360
NECK, THE SHOULDER, ARMPIT, DOWN

303
00:13:15,360 --> 00:13:16,480
THE SPINE AND AROUND THE

304
00:13:16,480 --> 00:13:17,120
KIDNEYS.

305
00:13:17,120 --> 00:13:19,400
WHITE FAT ALSO HAS A VISCERAL

306
00:13:19,400 --> 00:13:21,360
FLAVOR, AS IT WERE, AND THAT IS

307
00:13:21,360 --> 00:13:23,440
THE INTERNAL ORGANS, THEIR FAT,

308
00:13:23,440 --> 00:13:25,520
AND YOU CAN SEE HERE THERE'S

309
00:13:25,520 --> 00:13:32,080
EPICARDIAL, OMENTAL, MESENTERIC,

310
00:13:32,080 --> 00:13:36,400
PARIRENAL, GONADAL, THEY HAVE A

311
00:13:36,400 --> 00:13:36,840
DIFFERENT STRUCTURE.

312
00:13:36,840 --> 00:13:38,160
IN THIS THIRD VIEW, THE AXIAL

313
00:13:38,160 --> 00:13:39,320
VIEW, THIS IS A CUT THROUGH THE

314
00:13:39,320 --> 00:13:40,840
CENTER OF THE BODY, ONE CAN SEE

315
00:13:40,840 --> 00:13:43,520
THAT LOOKS CAN BE DECEIVING.

316
00:13:43,520 --> 00:13:46,120
SHOWN HERE IS A 37-YEAR-OLD MAN

317
00:13:46,120 --> 00:13:48,600
WHO HAS A WAIST CIRCUMFERENCE OF

318
00:13:48,600 --> 00:13:50,560
91 CENTIMETERS, THAT'S ABOUT

319
00:13:50,560 --> 00:13:51,000
36 INCHES.

320
00:13:51,000 --> 00:13:53,160
SHOWN HERE IS A MAN WHO'S

321
00:13:53,160 --> 00:13:54,960
82 YEARS OLD, WHOSE WAIST

322
00:13:54,960 --> 00:13:55,840
CIRCUMFERENCE IS THE SAME.

323
00:13:55,840 --> 00:13:57,160
BUT WHEN YOU LOOK INSIDE, YOU

324
00:13:57,160 --> 00:13:59,320
CAN SEE THERE'S FAR MORE

325
00:13:59,320 --> 00:14:00,640
SUBCUTANEOUS FAT, WHICH IS

326
00:14:00,640 --> 00:14:02,720
EITHER NEUTRAL OR EVEN POSITIVE

327
00:14:02,720 --> 00:14:03,520
FOR HEALTH.

328
00:14:03,520 --> 00:14:05,720
WHEREAS THIS INDIVIDUAL AT

329
00:14:05,720 --> 00:14:07,240
82 HAS MUCH MORE VISCERAL FAT,

330
00:14:07,240 --> 00:14:09,040
WHICH IS MORE LIKELY TO BE

331
00:14:09,040 --> 00:14:10,800
NEGATIVE IN TERMS OF AFFECTING

332
00:14:10,800 --> 00:14:13,520
HIS HEALTH.

333
00:14:13,520 --> 00:14:16,280
AND SO HUMAN WHITE FAT BEGINS TO

334
00:14:16,280 --> 00:14:17,640
DEVELOP IN THE SECOND TRIMESTER

335
00:14:17,640 --> 00:14:19,720
OF PREGNANCY, AND BY BIRTH, BOTH

336
00:14:19,720 --> 00:14:22,640
THE VISCERAL AND THE

337
00:14:22,640 --> 00:14:24,200
SUBCUTANEOUS DEPOTS ARE WELL

338
00:14:24,200 --> 00:14:24,800
ESTABLISHED.

339
00:14:24,800 --> 00:14:27,000
THE BROWN FAT OR BAT FIRST

340
00:14:27,000 --> 00:14:28,360
ARISES DURING THE LATE SECOND

341
00:14:28,360 --> 00:14:30,320
TRIMESTER, AND PROTECTS NEWBORNS

342
00:14:30,320 --> 00:14:31,600
FROM COLD WHILE THEY DEVELOP THE

343
00:14:31,600 --> 00:14:34,400
ABILITY TO SHIVER.

344
00:14:34,400 --> 00:14:36,640
IN LEAN ADULTS, THE ENTIRE WHITE

345
00:14:36,640 --> 00:14:39,360
FAT DEPOT RANGES FROM 20 TO

346
00:14:39,360 --> 00:14:40,640
30 KILOGRAMS IN WOMEN, THAT'S 30

347
00:14:40,640 --> 00:14:45,080
TO 40% OF TOTAL BODY MASS.

348
00:14:45,080 --> 00:14:46,720
AND IN MEN, 10 TO 20 KILOGRAMS

349
00:14:46,720 --> 00:14:49,240
OR 15 TO 25% OF TOTAL BODY MASS.

350
00:14:49,240 --> 00:14:52,400
SO YOU CAN APPRECIATE THAT THE

351
00:14:52,400 --> 00:14:53,840
ADIPOSE TISSUE DEPOT IS ONE OF

352
00:14:53,840 --> 00:14:55,760
THE LARGEST IF NOT THE LARGEST

353
00:14:55,760 --> 00:14:59,600
ORGAN IN THE BODY.

354
00:14:59,600 --> 00:15:01,800
NOW, IN THE ADIPOSE TISSUES, THE

355
00:15:01,800 --> 00:15:08,360
FORM FOLLOWS THE FUNCTION.

356
00:15:08,360 --> 00:15:11,840
WHITE ADIPO CYTES STORE ENERGY.

357
00:15:11,840 --> 00:15:15,240
IT HAS IMPORTANCE FOR THERMAL

358
00:15:15,240 --> 00:15:15,680
INSULATION.

359
00:15:15,680 --> 00:15:18,120
THEY'VE SHOWN THAT WHITE FAT IS

360
00:15:18,120 --> 00:15:19,680
IMPORTANT FOR KEEPING US WARM

361
00:15:19,680 --> 00:15:21,640
JUST BY FORMING A PROTECTIVE

362
00:15:21,640 --> 00:15:22,040
BLANKET.

363
00:15:22,040 --> 00:15:24,720
IN ADDITION, THERE IS MECHANICAL

364
00:15:24,720 --> 00:15:27,320
PROTECTION, AND WHITE FAT HAS

365
00:15:27,320 --> 00:15:29,560
DR. ARIAS MENTION IS INVOLVED AS

366
00:15:29,560 --> 00:15:30,920
AN ENDOCRINE ORGAN AND I'LL SHOW

367
00:15:30,920 --> 00:15:31,920
YOU MORE DETAILS ABOUT THAT.

368
00:15:31,920 --> 00:15:38,000
ON THE OTHER END ARE BRIGHT

369
00:15:38,000 --> 00:15:40,120
ADIPOCYTES, ORGANELLES INVOLVED

370
00:15:40,120 --> 00:15:42,800
IN ATP, CHEMICAL ENERGY AND ALSO

371
00:15:42,800 --> 00:15:45,240
HEAT AND THE BEIGE CELLS ARE IN

372
00:15:45,240 --> 00:15:45,440
BETWEEN.

373
00:15:45,440 --> 00:15:46,640
BOTH CELL TYPES, THE WHITE AND

374
00:15:46,640 --> 00:15:48,040
THE BROWN, CAN GENERATE HEAT AS

375
00:15:48,040 --> 00:15:49,440
I'LL SHOW YOU IN A MOMENT.

376
00:15:49,440 --> 00:15:51,680
SO THERE'S THE WHITE THAT STORE

377
00:15:51,680 --> 00:15:53,440
ENERGY, THE BROWN THAT EXPEND

378
00:15:53,440 --> 00:15:57,560
ENERGY, AND THEN THESE BEIGE OR

379
00:15:57,560 --> 00:15:58,680
BRITE CELLS IN BETWEEN.

380
00:15:58,680 --> 00:16:00,920
THEY RESPOND TO BOTH COLD AND

381
00:16:00,920 --> 00:16:04,520
ADRENERGIC STIMULATION, MEANING

382
00:16:04,520 --> 00:16:05,160
EPINEPHRINE, NOREPINEPHRINE, AND

383
00:16:05,160 --> 00:16:06,200
THEY CAN TRANSITION FROM AN

384
00:16:06,200 --> 00:16:09,880
ENERGY STORING FOR AN ENERGY

385
00:16:09,880 --> 00:16:10,800
EXPENDING TYPE OF CELL.

386
00:16:10,800 --> 00:16:11,760
HOW DOES IT HAPPEN?

387
00:16:11,760 --> 00:16:13,200
LET'S GO BACK TO YOUR HIGH

388
00:16:13,200 --> 00:16:14,600
SCHOOL CHEMISTRY AND

389
00:16:14,600 --> 00:16:17,880
BIOCHEMISTRY CLASSES, AND YOU

390
00:16:17,880 --> 00:16:24,960
CAN SEE HERE THAT TH THIS LEADSO

391
00:16:24,960 --> 00:16:26,440
THE PRODUCTION OF HYDROGEN ATOMS

392
00:16:26,440 --> 00:16:29,120
THAT GET SPLIT AND THE PROTONS

393
00:16:29,120 --> 00:16:32,800
GO TO THE INTERMEMBRANE SPACE,

394
00:16:32,800 --> 00:16:34,720
TAKEN UP BY OXYGEN TO MAKE

395
00:16:34,720 --> 00:16:36,400
WATER, AND THOSE PROTONS GO DOWN

396
00:16:36,400 --> 00:16:38,160
THESE PROTEINS HERE TO GENERATE

397
00:16:38,160 --> 00:16:39,760
ATP.

398
00:16:39,760 --> 00:16:45,400
BUT IN A BROWN ADIPOCYTE,

399
00:16:45,400 --> 00:16:46,600
UPC1 ALLOWS THOSE PROTONS TO

400
00:16:46,600 --> 00:16:47,880
RUSH RIGHT BACK IN TO THE

401
00:16:47,880 --> 00:16:48,600
MITOCHONDRIAL MATRIX.

402
00:16:48,600 --> 00:16:49,640
WHEN THAT HAPPENS, THERE'S NO

403
00:16:49,640 --> 00:16:51,400
LONGER A BACK PRESSURE OF

404
00:16:51,400 --> 00:16:54,200
PROTONS, AND THAT LEADS THE TCA

405
00:16:54,200 --> 00:16:55,320
CYCLE AND ELECTRON TRANSPORT

406
00:16:55,320 --> 00:16:56,960
CHAIN TO START GOING VERY, VERY

407
00:16:56,960 --> 00:16:58,080
QUICKLY, AND THAT GENERATES A

408
00:16:58,080 --> 00:17:00,080
LOT OF HEAT.

409
00:17:00,080 --> 00:17:01,880
BY ANALOGY, IF YOU WERE IN YOUR

410
00:17:01,880 --> 00:17:03,440
CAR AND YOU SHIFTED FROM DRIVE

411
00:17:03,440 --> 00:17:05,760
TO NEUTRAL AND THEN YOU PUT YOUR

412
00:17:05,760 --> 00:17:07,320
FOOT ON THE ACCELERATOR, A LOT

413
00:17:07,320 --> 00:17:08,520
OF FUEL WOULD GO THROUGH THE

414
00:17:08,520 --> 00:17:09,480
SYSTEM, THERE WOULDN'T BE ANY

415
00:17:09,480 --> 00:17:10,440
ENERGY BEING CONVERTED TO

416
00:17:10,440 --> 00:17:12,280
ANYTHING BUT HEAT.

417
00:17:12,280 --> 00:17:13,680
AND THERE ARE NEW PROCESSES OF

418
00:17:13,680 --> 00:17:17,240
GENERATING HEAT SHOWN BY BRUCE

419
00:17:17,240 --> 00:17:20,040
SPIEGELMAN WHERE THEY'VE SHOWN

420
00:17:20,040 --> 00:17:26,080
THERE'S ALSO SUPPER

421
00:17:26,080 --> 00:17:27,720
STOICHIOMETRIC FUTILE CYCLING.

422
00:17:27,720 --> 00:17:30,040
THERE'S ALSO SOMETHING CALLED

423
00:17:30,040 --> 00:17:32,640
TRIGLYCERIDE FATTY ACID CYCLING,

424
00:17:32,640 --> 00:17:35,680
BROKEN DOWN TO FATTY ACIDS BUT

425
00:17:35,680 --> 00:17:36,520
REBUILT, BROKEN DOWN AND REBUILT

426
00:17:36,520 --> 00:17:37,680
IN A CYCLE.

427
00:17:37,680 --> 00:17:39,320
ALL THAT'S HAPPENING HERE IS A

428
00:17:39,320 --> 00:17:40,200
FUTILE PRODUCTION OF HEAT.

429
00:17:40,200 --> 00:17:41,400
IF THAT'S WHAT THE CELL WANTS,

430
00:17:41,400 --> 00:17:42,680
IT'S VERY IMPORTANT, SO AS YOU

431
00:17:42,680 --> 00:17:43,960
CAN SEE HERE, THERE ARE SEVERAL

432
00:17:43,960 --> 00:17:45,280
MECHANISMS IN BOTH BROWN FAT AND

433
00:17:45,280 --> 00:17:49,080
WHITE FAT FOR GENERATING HEAT.

434
00:17:49,080 --> 00:17:50,080
WHICH ONES ARE ACTIVE, WHAT THE

435
00:17:50,080 --> 00:17:53,120
PROPORTIONS ARE, AND HOW DO YOU

436
00:17:53,120 --> 00:17:54,320
TURN THEM ON AND OFF ARE AREAS

437
00:17:54,320 --> 00:17:56,880
OF ACTIVE INVESTIGATION.

438
00:17:56,880 --> 00:17:58,000
NOW YOU HAVE TO REMEMBER THAT

439
00:17:58,000 --> 00:17:59,520
WHITE FAT AND BROWN FAT JUST

440
00:17:59,520 --> 00:18:00,840
LIKE EVERY OTHER TISSUE IN THE

441
00:18:00,840 --> 00:18:02,640
BODY ARE MADE UP OF A DIVERSITY

442
00:18:02,640 --> 00:18:04,680
OF CELL TYPES.

443
00:18:04,680 --> 00:18:05,600
WHITE FAT HAS MANY.

444
00:18:05,600 --> 00:18:13,120
AS YOU CAN SEE HERE, THERE ARE

445
00:18:13,120 --> 00:18:14,240
ADIPOCYTES, BUT WHITE FAT HAS A

446
00:18:14,240 --> 00:18:17,000
LOT OF MACROPHAGES, IMMUNE

447
00:18:17,000 --> 00:18:19,800
CELLS, T-CELLS, B CELLS, THERE'S

448
00:18:19,800 --> 00:18:20,920
ALSO BLOOD CELLS AND BLOOD

449
00:18:20,920 --> 00:18:21,360
VESSELS.

450
00:18:21,360 --> 00:18:24,600
THERE'S ALSO EOSINOPHILS,

451
00:18:24,600 --> 00:18:25,800
DENDRITIC CELLS FOR THE IMMUNE

452
00:18:25,800 --> 00:18:27,680
SYSTEM, AND THEN THERE'S THE ECM

453
00:18:27,680 --> 00:18:29,400
OR EXTRACELLULAR MATRIX AND

454
00:18:29,400 --> 00:18:32,560
THESE ARE PROTEINS AND OTHER

455
00:18:32,560 --> 00:18:35,680
KINDS OF MOLECULES THAT PROVIDE

456
00:18:35,680 --> 00:18:36,640
STRUCTURE AND SUPPORT BUT IT'S

457
00:18:36,640 --> 00:18:36,960
ACTIVE.

458
00:18:36,960 --> 00:18:38,800
THE ECM IS IN COMMUNICATION WITH

459
00:18:38,800 --> 00:18:43,640
THE CELLS WITHIN THISH TISSUE. .

460
00:18:43,640 --> 00:18:45,280
THERE ARE DOZENS OF FACTORS

461
00:18:45,280 --> 00:18:46,920
RELEASED AND THEY PROFOUNDLY

462
00:18:46,920 --> 00:18:48,080
IMPACT ORGANS THROUGHOUT THE

463
00:18:48,080 --> 00:18:48,400
BODY.

464
00:18:48,400 --> 00:18:49,840
SHOWN HERE ARE FACTORS RELEASED

465
00:18:49,840 --> 00:18:52,960
BY THE WHITE FAT, BOTH THE WHITE

466
00:18:52,960 --> 00:18:54,480
ADIPOCYTES AND THE OTHER CELLS.

467
00:18:54,480 --> 00:19:00,600
THERE ARE ADIPOKINES, YOU'VE

468
00:19:00,600 --> 00:19:03,040
HEARD OF LEPTIN PERHAPS, THERE

469
00:19:03,040 --> 00:19:05,680
ARE MANY AS WELL, CYTOKINES,

470
00:19:05,680 --> 00:19:07,280
ENZYMES, COMPOUNDS INVOLVED IN

471
00:19:07,280 --> 00:19:09,960
LID I ID TRANSPORT AND OTHER

472
00:19:09,960 --> 00:19:10,680
FACTORS AS WELL.

473
00:19:10,680 --> 00:19:11,720
SO THERE'S OVER 50 AND THESE ARE

474
00:19:11,720 --> 00:19:12,880
JUST A FEW HERE.

475
00:19:12,880 --> 00:19:14,480
AND THEY AFFECT EVERY ORGAN IN

476
00:19:14,480 --> 00:19:15,480
THE BODY PRACTICALLY.

477
00:19:15,480 --> 00:19:19,040
IN THE BRAIN, THE HORMONES IN

478
00:19:19,040 --> 00:19:21,320
THE WHITE FAT CAN FEEDBACK AND

479
00:19:21,320 --> 00:19:24,760
IMPACT APPETITE, SENSES OF

480
00:19:24,760 --> 00:19:26,560
SATIETY, ENERGY EXPENDITURE, THE

481
00:19:26,560 --> 00:19:27,960
IMMUNE SYSTEM, THE

482
00:19:27,960 --> 00:19:30,440
CARDIOVASCULAR SYSTEM, LIVER,

483
00:19:30,440 --> 00:19:32,000
PANCREAS, THE GASTROINTESTINAL

484
00:19:32,000 --> 00:19:35,800
TRACT IN TERMS OF AB SORNTION, D

485
00:19:35,800 --> 00:19:36,960
MUSCLES AS WELL JUST TO NAME A

486
00:19:36,960 --> 00:19:38,240
FEW OF THE ORGAN SYSTEMS

487
00:19:38,240 --> 00:19:41,480
INVOLVED.

488
00:19:41,480 --> 00:19:43,880
NOW THE ROLES OF HUMAN BROWN

489
00:19:43,880 --> 00:19:44,520
ADIPOSE TISSUE ARE ONLY

490
00:19:44,520 --> 00:19:46,880
BEGINNING TO BE DISCOVERED.

491
00:19:46,880 --> 00:19:48,080
WHAT'S FASCINATING TO ME IS THAT

492
00:19:48,080 --> 00:19:50,120
THE BROWN ADIPOCYTES ARE PACKED

493
00:19:50,120 --> 00:19:51,120
WITH MITOCHONDRIA.

494
00:19:51,120 --> 00:19:54,520
THERE ARE SACKS OF MITOCHONDRIA.

495
00:19:54,520 --> 00:19:56,680
SHOWN HERE IS AN EOSINE STAIN

496
00:19:56,680 --> 00:19:59,120
AND YOU CAN SEE THESE ARE

497
00:19:59,120 --> 00:19:59,920
INDIVIDUAL CELLS I'M DRAWING OUT

498
00:19:59,920 --> 00:20:01,600
AND THESE ARE THE LIPID

499
00:20:01,600 --> 00:20:02,320
DROPLETS.

500
00:20:02,320 --> 00:20:04,400
IF YOU USE A HIGHER

501
00:20:04,400 --> 00:20:06,880
MAGNIFICATION, YOU CAN SEE ONE

502
00:20:06,880 --> 00:20:13,840
BROWN AD ADIPOCYTE, HERE ARE LID

503
00:20:13,840 --> 00:20:15,840
DROPLET'S USED AS FUEL, AND

504
00:20:15,840 --> 00:20:19,200
EVERY OTHER LITTLE BROWN CIRCLE

505
00:20:19,200 --> 00:20:22,160
HERE, EVERY LITTLE GREY SITE IS

506
00:20:22,160 --> 00:20:24,080
A MITOCHONDRIAN.

507
00:20:24,080 --> 00:20:27,200
NOW THE MAXIMUM DETECTABLE BROWN

508
00:20:27,200 --> 00:20:29,080
ADIPOSE TISSUE MASS ON A HUMAN

509
00:20:29,080 --> 00:20:30,960
WE'VE SEEN SO FAR IS ROUGHLY

510
00:20:30,960 --> 00:20:32,720
1-KILOGRAM OR JUST OVER 2 POUNDS

511
00:20:32,720 --> 00:20:34,440
BUT USUALLY BASED ON OUR IMAGING

512
00:20:34,440 --> 00:20:36,320
IT'S FROM 50 TO 500 GRAMS, WHICH

513
00:20:36,320 --> 00:20:40,080
IS LESS THAN A POUND, .1 TO .5%

514
00:20:40,080 --> 00:20:43,280
OF TOTAL BODY MASS AND .2 TO 3%

515
00:20:43,280 --> 00:20:44,240
OF TOTAL ADIPOSE TISSUE.

516
00:20:44,240 --> 00:20:46,120
AND WE'RE JUST BEGINNING TO

517
00:20:46,120 --> 00:20:48,440
IDENTIFY THE ADD POE KINES, THE

518
00:20:48,440 --> 00:20:49,640
HORMONES RELEASED BY BROWN

519
00:20:49,640 --> 00:20:50,240
ADIPOSE TISSUE.

520
00:20:50,240 --> 00:20:51,160
CAN YOU SEE SOME IN THE DIAGRAM

521
00:20:51,160 --> 00:20:51,720
OVER HERE.

522
00:20:51,720 --> 00:20:57,120
I LIKE TO FOCUS IN PARTICULAR ON

523
00:20:57,120 --> 00:21:01,480
12, 13DIHOME AND 12HEPE, AND

524
00:21:01,480 --> 00:21:04,080
THESE HAVE BEEN IDENTIFIED

525
00:21:04,080 --> 00:21:06,160
SAYING A COLLEAGUE AND

526
00:21:06,160 --> 00:21:08,440
COLLABORATOR AT JOSLIN DIABETES

527
00:21:08,440 --> 00:21:09,880
CENTER IN BOSTON, AND THESE GO

528
00:21:09,880 --> 00:21:11,040
TO OTHER TISSUES AND CAUSE

529
00:21:11,040 --> 00:21:12,480
RELEASE OF THE UPTAKE OF FATTY

530
00:21:12,480 --> 00:21:15,800
ACIDS AND GLUCOSE INTO THOSE

531
00:21:15,800 --> 00:21:18,960
TISSUES.

532
00:21:18,960 --> 00:21:21,440
THE FLIP SIDE IS WHEN TR

533
00:21:21,440 --> 00:21:22,840
TRIGLYCERIDES ARE IN EXCESS OR

534
00:21:22,840 --> 00:21:24,600
STORED INCORRECTLY, IT CAN LEAD

535
00:21:24,600 --> 00:21:25,320
TO COMPLICATIONS.

536
00:21:25,320 --> 00:21:27,240
SHOWN HERE IS A DIAGRAM

537
00:21:27,240 --> 00:21:29,720
DISPLAYING THE VARIOUS

538
00:21:29,720 --> 00:21:30,920
COMPLICATIONS IN THE DIFFERENT

539
00:21:30,920 --> 00:21:33,400
ORGAN SYSTEMS FROM OBESITY.

540
00:21:33,400 --> 00:21:36,160
AND HOW THIS HAPPENS IS THAT

541
00:21:36,160 --> 00:21:37,800
WHITE ADIPOCYTES CAN SWELL ON

542
00:21:37,800 --> 00:21:42,200
THE BASELINE OF ROUGHLY 30, 40

543
00:21:42,200 --> 00:21:43,320
40 MICRONS ACROSS TO OVER

544
00:21:43,320 --> 00:21:43,880
100 MICRONS.

545
00:21:43,880 --> 00:21:45,840
THAT'S A 10 TIMES INCREASE IN

546
00:21:45,840 --> 00:21:46,080
VOLUME.

547
00:21:46,080 --> 00:21:49,560
NOW THE ANATOMICAL LOCATION AND

548
00:21:49,560 --> 00:21:51,360
GENETICS LARGELY DETERMINE THE

549
00:21:51,360 --> 00:21:53,720
PROPORTIONAL INCREASE IN THE

550
00:21:53,720 --> 00:21:54,280
ADIPOCYTE SIZE AND NUMBER AS

551
00:21:54,280 --> 00:21:55,480
WELL AS THE PHYSIOLOGICAL

552
00:21:55,480 --> 00:21:59,960
RESPONSES THAT CAN BE SEEN.

553
00:21:59,960 --> 00:22:03,080
SO FOR EXAMPLE, PEOPLE WHOSE

554
00:22:03,080 --> 00:22:05,320
SUBCUTANEOUS DEPOTS MAINTAIN

555
00:22:05,320 --> 00:22:08,920
SMALLER ADIPOCYTES HAVE FEWER

556
00:22:08,920 --> 00:22:09,560
METABOLIC COMPLICATIONS.

557
00:22:09,560 --> 00:22:11,560
OTHERS HAVE A GENETIC INABILITY

558
00:22:11,560 --> 00:22:14,280
TO RECRUIT NEW ADIPOCYTES SO

559
00:22:14,280 --> 00:22:15,360
THEY INSTEAD GO TO THE REST OF

560
00:22:15,360 --> 00:22:17,200
THE BODY AND CAUSE ADDITIONAL

561
00:22:17,200 --> 00:22:20,800
COMPLICATIONS SUCH AS STROKE,

562
00:22:20,800 --> 00:22:22,720
CATARACTS, PROBLEMS IN THE

563
00:22:22,720 --> 00:22:25,000
LUNGS, GASTROINTESTINAL TRACT,

564
00:22:25,000 --> 00:22:27,720
CARDIOVASCULAR WE KNOW ABOUT,

565
00:22:27,720 --> 00:22:28,920
MUSCULOSKELETAL SYSTEM AS WELL.

566
00:22:28,920 --> 00:22:30,680
SO ULTIMATELY, WHAT HAPPENS IS

567
00:22:30,680 --> 00:22:32,880
THAT WHEN THAT WHITE FAT BECOMES

568
00:22:32,880 --> 00:22:36,280
VERY LARGE OR HYPERTROPHIC, AND

569
00:22:36,280 --> 00:22:37,160
EXPANDS, THE PROBLEM IS THAT

570
00:22:37,160 --> 00:22:38,200
THERE'S NOT ENOUGH OXYGEN

571
00:22:38,200 --> 00:22:39,400
GETTING TO THE CELLS.

572
00:22:39,400 --> 00:22:42,520
THERE ARE OTHER PROBLEMS WITH

573
00:22:42,520 --> 00:22:43,480
THE -- INSIDE THE CELLS AS WELL,

574
00:22:43,480 --> 00:22:44,960
FOR EXAMPLE, THERE'S THE

575
00:22:44,960 --> 00:22:47,760
UNFOLDED PROTEIN RESPONSE IN THE

576
00:22:47,760 --> 00:22:49,960
ENDO PLASMIC RETICULUM, BUT IT'S

577
00:22:49,960 --> 00:22:51,480
THE HYPOXIA THAT'S A REAL

578
00:22:51,480 --> 00:22:53,440
PROBLEM, BECAUSE WHAT HAPPENS

579
00:22:53,440 --> 00:22:56,840
IS, THAT HYPOXIA IS A BIOLOGICAL

580
00:22:56,840 --> 00:22:58,440
RED ALERT FOR THE CELLS AND IT

581
00:22:58,440 --> 00:22:59,800
ALTERS THE EXPRESSION OF MORE

582
00:22:59,800 --> 00:23:00,720
THAN A THOUSAND GENES AND

583
00:23:00,720 --> 00:23:02,000
TRIGGERS A SERIES OF

584
00:23:02,000 --> 00:23:03,240
INTERCONNECTED RESPONSES THAT

585
00:23:03,240 --> 00:23:04,920
LEAD TO LOCAL RESISTANCE TO

586
00:23:04,920 --> 00:23:07,000
INSULIN SIGNALING, INCREASED

587
00:23:07,000 --> 00:23:07,760
INFLAMMATION, AND CELLULAR

588
00:23:07,760 --> 00:23:13,480
DAMAGE.

589
00:23:13,480 --> 00:23:15,120
HOWEVER, AS THE TITLE INDICATES,

590
00:23:15,120 --> 00:23:17,760
IT'S REALLY USEFUL TO

591
00:23:17,760 --> 00:23:18,760
CONCEPTUALIZE OBESITY AS A

592
00:23:18,760 --> 00:23:19,720
DISEASE ORIGINATING IN THE BRAIN

593
00:23:19,720 --> 00:23:21,960
THAT IS MANIFESTED MORE AS AN

594
00:23:21,960 --> 00:23:24,120
EXCESS OF WHITE ADIPOSE TISSUE

595
00:23:24,120 --> 00:23:25,560
AND A DYSFUNCTIONAL BROWN

596
00:23:25,560 --> 00:23:26,840
ADIPOSE TISSUE.

597
00:23:26,840 --> 00:23:28,040
AND STUDYS HAVE SHOWN THAT

598
00:23:28,040 --> 00:23:30,280
THERE'S A PERNICIOUS CYCLE THAT

599
00:23:30,280 --> 00:23:31,560
ACCELERATES THE DEVELOPMENT OF

600
00:23:31,560 --> 00:23:32,960
OBESITY ONCE A PERSON HAS BEGUN

601
00:23:32,960 --> 00:23:35,880
TO GAIN WEIGHT.

602
00:23:35,880 --> 00:23:37,160
AND IN THE BRAIN IN PARTICULAR,

603
00:23:37,160 --> 00:23:39,960
IT'S THE HYPOTHALAMIC REGION

604
00:23:39,960 --> 00:23:41,000
THAT'S OF INCREASING INTEREST

605
00:23:41,000 --> 00:23:42,520
BECAUSE IT INTEGRATES MULTIPLE

606
00:23:42,520 --> 00:23:44,160
PHYSIOLOGICAL SIGNALS FROM THE

607
00:23:44,160 --> 00:23:46,040
BODY, AND THEN TRANSMITS THEM TO

608
00:23:46,040 --> 00:23:47,920
DIFFERENT BRAIN REGIONS AND

609
00:23:47,920 --> 00:23:49,440
COORDINATE THE REGULATION OF

610
00:23:49,440 --> 00:23:51,080
DIVERSE PROCESSES, INCLUDING

611
00:23:51,080 --> 00:23:57,160
BODY TEMPERATURE AND FEEDING.

612
00:23:57,160 --> 00:24:00,480
AS YOU CAN IMAGINE, CHILLED WITH

613
00:24:00,480 --> 00:24:04,800
OBESITY ARE AT RISK AS SHOWN BY

614
00:24:04,800 --> 00:24:06,080
THIS DIAGRAM AND EVEN MORE

615
00:24:06,080 --> 00:24:07,240
TROUBLING IS THE RATES OF

616
00:24:07,240 --> 00:24:08,600
OBESITY ARE INCREASING MUCH

617
00:24:08,600 --> 00:24:09,920
FASTER AMONG CHILDREN THAN AMONG

618
00:24:09,920 --> 00:24:10,480
ADULTS.

619
00:24:10,480 --> 00:24:12,320
CERTAINLY IN OUR COUNTRY AND

620
00:24:12,320 --> 00:24:12,800
WORLDWIDE.

621
00:24:12,800 --> 00:24:14,040
AND CHILDREN WITH OBESITY ARE

622
00:24:14,040 --> 00:24:16,400
MORE LIKELY TO BECOME ADULTS WHO

623
00:24:16,400 --> 00:24:17,960
HAVE A HIGH RISK OF SEVERE

624
00:24:17,960 --> 00:24:18,760
HEALTH COMPLICATIONS.

625
00:24:18,760 --> 00:24:21,400
WE NEED TO DO SOMETHING ABOUT

626
00:24:21,400 --> 00:24:22,200
IT.

627
00:24:22,200 --> 00:24:23,640
AND I'M GOING TO GO TO ONE PART

628
00:24:23,640 --> 00:24:25,160
OF THAT AND THAT'S ON THE BROWN

629
00:24:25,160 --> 00:24:26,200
ADIPOSE TISSUE, SOMETHING THAT

630
00:24:26,200 --> 00:24:27,760
I'VE BEEN STUDYING FOR NEARLY

631
00:24:27,760 --> 00:24:29,960
TWO DECADES, AND SO I'M GOING TO

632
00:24:29,960 --> 00:24:33,080
GO INTO SOME RELEVANT RECENT BAT

633
00:24:33,080 --> 00:24:33,320
HISTORY.

634
00:24:33,320 --> 00:24:35,600
AND THE MODERN ERA OF BAT

635
00:24:35,600 --> 00:24:39,760
STUDIES BEGAN IN 2002, AND AN

636
00:24:39,760 --> 00:24:40,960
ENTIRELY DIFFERENT AREA FROM

637
00:24:40,960 --> 00:24:41,760
METABOLISM AND THAT IS IN THE

638
00:24:41,760 --> 00:24:43,920
AREA OF RADIOLOGY AND CANCER

639
00:24:43,920 --> 00:24:44,280
SURVEILLANCE.

640
00:24:44,280 --> 00:24:45,760
AND IT WAS FOUND THAT ADULT

641
00:24:45,760 --> 00:24:48,960
HUMANS HAD SOMETHING -- A

642
00:24:48,960 --> 00:24:50,080
GLUCOSE-AVID ADIPOSE TISSUE,

643
00:24:50,080 --> 00:24:52,120
WHICH SUGGESTED THERE MIGHT BE

644
00:24:52,120 --> 00:24:52,520
FUNCTIONAL BAT.

645
00:24:52,520 --> 00:24:54,160
AND THE REASON THIS WAS POSSIBLE

646
00:24:54,160 --> 00:24:56,520
IS THAT PREVIOUSLY, PEOPLE WERE

647
00:24:56,520 --> 00:24:58,920
USING COMPUTED TOMOGRAPHY,

648
00:24:58,920 --> 00:25:00,040
THAT'S A THREE-DIMENSIONAL X-RAY

649
00:25:00,040 --> 00:25:01,360
THAT GIVES STRUCTURE AS AN

650
00:25:01,360 --> 00:25:02,600
EXAMPLE SHOWN HERE, HERE'S THE

651
00:25:02,600 --> 00:25:04,160
HEART, HERE'S THE LIVER, THE

652
00:25:04,160 --> 00:25:04,400
LUNGS.

653
00:25:04,400 --> 00:25:06,560
THERE'S THE RIBCAGE OF THIS

654
00:25:06,560 --> 00:25:07,240
32-YEAR-OLD MAN.

655
00:25:07,240 --> 00:25:08,400
AND THEN THERE'S SOMETHING

656
00:25:08,400 --> 00:25:10,480
CALLED PET IMAGING, THAT'S

657
00:25:10,480 --> 00:25:12,280
POSITRON EMISSION TOMOGRAPHY,

658
00:25:12,280 --> 00:25:13,640
ONE CAN LABEL GLUCOSE, FOR

659
00:25:13,640 --> 00:25:15,320
EXAMPLE, AS A TRACER, AND IT

660
00:25:15,320 --> 00:25:16,040
SHOWS WHAT'S FUNCTIONALLY

661
00:25:16,040 --> 00:25:16,640
ACTIVE.

662
00:25:16,640 --> 00:25:17,440
FOR EXAMPLE, IN THIS PERSON OVER

663
00:25:17,440 --> 00:25:19,280
HERE, YOU CAN SEE THERE'S A LOT

664
00:25:19,280 --> 00:25:20,840
OF GLUCOSE GOING INTO THE HEART,

665
00:25:20,840 --> 00:25:23,640
TAKING UP A LOT OF GLUCOSE AS IT

666
00:25:23,640 --> 00:25:24,400
PUMPS, IT GOES INTO THE BRAIN

667
00:25:24,400 --> 00:25:25,800
AND THEN CURIOUSLY INTO THESE

668
00:25:25,800 --> 00:25:29,120
CELLS THAT ARE LYING IN THE

669
00:25:29,120 --> 00:25:29,640
UPPER CHEST.

670
00:25:29,640 --> 00:25:31,720
THE ABILITY TO FUSE THE CT AND

671
00:25:31,720 --> 00:25:33,760
PET TOGETHER INTO A PET/C T

672
00:25:33,760 --> 00:25:35,000
OPENED THE DOORS TO AN ENORMOUS

673
00:25:35,000 --> 00:25:36,480
AMOUNT OF EXCITEMENT AND

674
00:25:36,480 --> 00:25:38,960
RESEARCH ACTIVITY BECAUSE IT WAS

675
00:25:38,960 --> 00:25:40,240
DETERMINED THAT THESE CELLS,

676
00:25:40,240 --> 00:25:41,200
THESE TISSUES THAT WERE TAKING

677
00:25:41,200 --> 00:25:43,000
UP A LOT OF THE GLUCOSE AND THE

678
00:25:43,000 --> 00:25:44,280
IMAGE WAS FUSED, IT TURNED OUT

679
00:25:44,280 --> 00:25:44,840
IT WAS FAT.

680
00:25:44,840 --> 00:25:47,760
IT WASN'T MUSCLE, IT WASN'T

681
00:25:47,760 --> 00:25:48,600
TUMOR.

682
00:25:48,600 --> 00:25:49,880
SO THAT SUGGESTS THERE WAS

683
00:25:49,880 --> 00:25:50,800
FUNCTIONAL BROWN FAT WHICH HAD

684
00:25:50,800 --> 00:25:52,680
BEEN DENIED IN HUMANS.

685
00:25:52,680 --> 00:25:54,280
I WAS VERY EXCITED BY THIS SO AT

686
00:25:54,280 --> 00:25:57,760
THE END OF MY ENDOCRINE

687
00:25:57,760 --> 00:25:59,600
FELLOWSHIP, I PRESENTED THE

688
00:25:59,600 --> 00:26:00,520
SLIDES SAYING THERE MIGHT BE

689
00:26:00,520 --> 00:26:02,200
BROWN FAT IN ADULT HUMANS.

690
00:26:02,200 --> 00:26:03,520
HOW EXCITING WOULD THAT BE?

691
00:26:03,520 --> 00:26:06,720
WELL, I WAS CHALLENGED AT THE

692
00:26:06,720 --> 00:26:08,920
END OF THE TALK AND I WROTE BACK

693
00:26:08,920 --> 00:26:10,280
IN EMAIL TO ONE OF THE

694
00:26:10,280 --> 00:26:11,760
CHALLENGERS AND SAID YOU BELIEVE

695
00:26:11,760 --> 00:26:12,800
THERE'S NO SIGNIFICANT BROWN FAT

696
00:26:12,800 --> 00:26:14,120
IN ADULT HUMANS AND THAT WHAT

697
00:26:14,120 --> 00:26:16,040
WE'RE SEEING ON THOSE PET/CT

698
00:26:16,040 --> 00:26:17,680
SCANS IS NOT BROWN FAT?

699
00:26:17,680 --> 00:26:19,520
AND HE WROTE BACK, YES, THAT'S

700
00:26:19,520 --> 00:26:20,840
PRETTY MUCH IT.

701
00:26:20,840 --> 00:26:22,280
I WILL BE VERY SURPRISED IF

702
00:26:22,280 --> 00:26:24,280
THOSE PET IMAGES WERE BROWN FAT

703
00:26:24,280 --> 00:26:25,120
DEPOSITS.

704
00:26:25,120 --> 00:26:26,600
THIS IS A HARVARD MEDICAL SCHOOL

705
00:26:26,600 --> 00:26:27,400
ENDOCRINOLOGIST SO THIS WAS

706
00:26:27,400 --> 00:26:28,640
REALLY IMPORTANT AND SOMEWHAT

707
00:26:28,640 --> 00:26:31,760
DISPERIODISSPIRITTING AT THE TI.

708
00:26:31,760 --> 00:26:33,280
BUT I RECEIVED ENCOURAGEMENT

709
00:26:33,280 --> 00:26:35,720
FROM SOMEBODY ELSE, A HARVARD

710
00:26:35,720 --> 00:26:36,320
MEDICAL SCHOOL RADIOLOGIST.

711
00:26:36,320 --> 00:26:38,160
I WROTE TO HIM AND SAID, IN

712
00:26:38,160 --> 00:26:40,000
THOSE FDG-PET SCANS YOU VERY

713
00:26:40,000 --> 00:26:41,680
OFTEN SEE FALSE POSITIVE SIGNALS

714
00:26:41,680 --> 00:26:42,520
FROM BROWN FAT.

715
00:26:42,520 --> 00:26:44,400
HOW DO WE KNOW THAT IT'S BROWN

716
00:26:44,400 --> 00:26:44,840
FAT?

717
00:26:44,840 --> 00:26:46,360
AND HE SAID, BECAUSE EVERYONE

718
00:26:46,360 --> 00:26:47,280
SAYS SO.

719
00:26:47,280 --> 00:26:48,360
SO THIS WAS THE STATE OF THE

720
00:26:48,360 --> 00:26:51,120
FIELD BACK IN 2006.

721
00:26:51,120 --> 00:26:52,280
AND LED US TO GET WORKING AND

722
00:26:52,280 --> 00:26:55,080
SHOW THAT WHAT WE WERE SEEING ON

723
00:26:55,080 --> 00:26:57,200
THOSE IMAGES TRULY WAS BROWN

724
00:26:57,200 --> 00:26:58,040
FAT.

725
00:26:58,040 --> 00:26:58,920
IT WASN'T JUST OUR GROUP.

726
00:26:58,920 --> 00:27:00,800
FIVE PAPERS CAME OUT IN THE SPAN

727
00:27:00,800 --> 00:27:03,160
OF ONE MONTH IN 20 2009 PUBLISH

728
00:27:03,160 --> 00:27:04,080
DOLLARS IN THE NEW ENGLAND

729
00:27:04,080 --> 00:27:05,760
JOURNAL OF MEDICINE AND OTHER

730
00:27:05,760 --> 00:27:06,920
SOURCES AND IT WAS FOUND THAT

731
00:27:06,920 --> 00:27:09,600
BROWN FAT WAS PREDOMINANTLY IN A

732
00:27:09,600 --> 00:27:10,600
FEW SPECIFIC REGIONS OF THE

733
00:27:10,600 --> 00:27:13,160
BODY, NOT EVERYWHERE, BUT WE CAN

734
00:27:13,160 --> 00:27:15,000
FINALLY MEASURE IT

735
00:27:15,000 --> 00:27:17,440
NON-INVASIVELY VIA PET/CT AND

736
00:27:17,440 --> 00:27:19,040
FINALLY UNDERSTAND THE TISSUE IN

737
00:27:19,040 --> 00:27:19,320
REALTIME.

738
00:27:19,320 --> 00:27:21,280
WHAT WE LEARN FUNCTIONALLY, IT

739
00:27:21,280 --> 00:27:22,600
PROTECTS AGAINST THE COLD

740
00:27:22,600 --> 00:27:25,800
ACUTELY AND CHRONICALLY,

741
00:27:25,800 --> 00:27:27,560
NON-SHIVERING THERM ROW GENESIS.

742
00:27:27,560 --> 00:27:30,200
NOW NOISE THERE'S A TISSUE

743
00:27:30,200 --> 00:27:32,400
KEEPING US WARM WITHOUT MAKING

744
00:27:32,400 --> 00:27:33,680
US FEEL UNCOMFORTABLE.

745
00:27:33,680 --> 00:27:36,480
PEOPLE WITH BROWN FAT BASED ON

746
00:27:36,480 --> 00:27:37,680
RETROSPECTIVE BACKWARD LOOKING

747
00:27:37,680 --> 00:27:39,000
STUDIES, PEOPLE WITH MORE BROWN

748
00:27:39,000 --> 00:27:40,640
FAT WERE FREQUENTLY FEMALE,

749
00:27:40,640 --> 00:27:42,600
YOUNGER, LEANER, AND NOT TAKING

750
00:27:42,600 --> 00:27:43,840
BETA-BLOCKER MEDICATIONS, WHICH

751
00:27:43,840 --> 00:27:47,120
MEANS THAT BROWN FAT COULD BE

752
00:27:47,120 --> 00:27:48,320
AFFECTED BY MEDICATIONS.

753
00:27:48,320 --> 00:27:50,160
AND FINALLY, IT APPEARED THAT

754
00:27:50,160 --> 00:27:51,720
NEARLY EVERY ADULT HUMAN HAS

755
00:27:51,720 --> 00:27:53,640
SOME BROWN FAT.

756
00:27:53,640 --> 00:27:58,240
IT'IT'S REALLY THERE, AND THEY E

757
00:27:58,240 --> 00:27:59,880
A BIG IMPACT ON OUR PHYSIOLOGY.

758
00:27:59,880 --> 00:28:01,240
AND IN THE 10 YEARS SINCE THEN,

759
00:28:01,240 --> 00:28:02,880
A LOT OF EXCITING RESEARCH HAS

760
00:28:02,880 --> 00:28:05,880
BEEN DONE USING RODENT MODELS.

761
00:28:05,880 --> 00:28:07,080
SHOWN HERE IS INFORMATION ABOUT

762
00:28:07,080 --> 00:28:08,880
CHOLESTEROL PROFILE AND

763
00:28:08,880 --> 00:28:09,960
CARDIOVASCULAR RISK, DONE BY

764
00:28:09,960 --> 00:28:12,880
GROUPS LED BY PATRICK RENSEN IN

765
00:28:12,880 --> 00:28:18,320
THE NETHERLANDS, VIRTANEN IN

766
00:28:18,320 --> 00:28:19,440
FINLAND.

767
00:28:19,440 --> 00:28:20,360
BASICALLY WHAT WE SHOWED IN A

768
00:28:20,360 --> 00:28:21,360
PARTICULAR MOUSE MODEL, THAT

769
00:28:21,360 --> 00:28:23,360
BROWN FAT ACTIVATION INCREASES

770
00:28:23,360 --> 00:28:27,360
ENERGY EXPENDITURE BUT IT ALSO

771
00:28:27,360 --> 00:28:28,000
DECREASES PLASMA TRIGLYCERIDES

772
00:28:28,000 --> 00:28:29,840
AND REDUCES CHOLESTEROL LEVELS,

773
00:28:29,840 --> 00:28:34,400
LEADING TO HEALTH BENEFIT.

774
00:28:34,400 --> 00:28:37,480
THEN IN A SERIES OF STUDIES

775
00:28:37,480 --> 00:28:38,960
CONDUCTED IN GERMANY, THEY

776
00:28:38,960 --> 00:28:43,920
SHOWED A FASCINATING NEW AXIS, A

777
00:28:43,920 --> 00:28:46,320
BROWN FAT, LIVER, GUT MICROBIOME

778
00:28:46,320 --> 00:28:47,120
AXIS.

779
00:28:47,120 --> 00:28:48,800
SO WHAT HAPPENS IS, COLD

780
00:28:48,800 --> 00:28:53,080
EXPOSURE ACTIVATES BROWP FAT, B,

781
00:28:53,080 --> 00:28:55,560
AND CAUSES THE FAT IN OUR FOOT

782
00:28:55,560 --> 00:28:59,040
AFTER EATING, POSE PRANDIALLY,

783
00:28:59,040 --> 00:29:01,040
UPTAKE IN BROWN FAT.

784
00:29:01,040 --> 00:29:03,040
THIS ACCELERATES CHOLESTEROL

785
00:29:03,040 --> 00:29:04,840
UPTAKE INTO THE LIVER.

786
00:29:04,840 --> 00:29:06,680
BAT ACTIVATION CAUSES INCREASED

787
00:29:06,680 --> 00:29:07,960
SYNTHESIS OF BILE ACIDS, WHICH

788
00:29:07,960 --> 00:29:12,320
YOU MAY KNOW OF AS SMALL

789
00:29:12,320 --> 00:29:14,360
DETERGENTS MADE BY THE BODY THAT

790
00:29:14,360 --> 00:29:15,080
HELP ABSORB FAT.

791
00:29:15,080 --> 00:29:15,720
THEY DO MORE THAN THAT.

792
00:29:15,720 --> 00:29:17,360
THEY GO INTO THE GUT AND AFFECT

793
00:29:17,360 --> 00:29:20,640
THE MICROBIOME AND THAT'S VERY

794
00:29:20,640 --> 00:29:24,520
IMPORTANT FOR OVERALL HEALTH.

795
00:29:24,520 --> 00:29:27,080
THEN A RETROSPECTIVE STUDY

796
00:29:27,080 --> 00:29:30,480
CONDUCTED BY PAUL COHEN'S GROUP

797
00:29:30,480 --> 00:29:31,440
PUBLISHED TWO YEARS AGO, THEY

798
00:29:31,440 --> 00:29:34,000
LOOKED AT OVER 50,000 PATIENTS

799
00:29:34,000 --> 00:29:35,200
AND FOUND THAT PEOPLE WITH BROWN

800
00:29:35,200 --> 00:29:38,800
FAT HAD LOWER RATES OF TYPE

801
00:29:38,800 --> 00:29:40,400
2 DIABETES, DYSLIPIDEMIA,

802
00:29:40,400 --> 00:29:42,360
CORONARY ARTERY DISEASE,

803
00:29:42,360 --> 00:29:43,240
CARDIOVASCULAR DISEASE,

804
00:29:43,240 --> 00:29:44,640
CONGESTIVE HEART FAILURE, AND

805
00:29:44,640 --> 00:29:47,640
HYPERTENSION.

806
00:29:47,640 --> 00:29:49,200
SO THEY SAID THEIR STUDY

807
00:29:49,200 --> 00:29:50,520
INDICATES AN IMPORTANT

808
00:29:50,520 --> 00:29:56,080
CONTRIBUTION OF BAT IN HUMANS TO

809
00:29:56,080 --> 00:29:56,960
CARDIOMETABOLIC HEALTH AND

810
00:29:56,960 --> 00:29:58,400
SUGGESTS THAT BAT HAS

811
00:29:58,400 --> 00:29:59,600
THERAPEUTIC POTENTIAL IN HUMANS.

812
00:29:59,600 --> 00:30:01,080
WE'RE IN THE RIGHT PLACE.

813
00:30:01,080 --> 00:30:04,680
SO WHEN ONE DISCOVERS A NEW

814
00:30:04,680 --> 00:30:06,200
FUNCTIONAL ORGAN IN HUMANS THAT

815
00:30:06,200 --> 00:30:07,920
HAS THE POTENTIAL OF IMPACTING

816
00:30:07,920 --> 00:30:09,240
HUMAN HEALTH NEED TO BUILD A

817
00:30:09,240 --> 00:30:10,840
RESEARCH PLATFORM THIS IS WHAT

818
00:30:10,840 --> 00:30:11,560
WE'VE DONE.

819
00:30:11,560 --> 00:30:14,520
OURS RESTS ON THREE PILLARS.

820
00:30:14,520 --> 00:30:16,240
NONINVASIVE IMAGING, INTEGRATIVE

821
00:30:16,240 --> 00:30:17,680
PHYSIOLOGY, AND THERAPEUTICS,

822
00:30:17,680 --> 00:30:20,120
AND ALL THREE IMPACT EACH OTHER.

823
00:30:20,120 --> 00:30:21,920
SO ON THE IMAGING SIDE, WE WANT

824
00:30:21,920 --> 00:30:23,440
TO MEASURE BROWN FAT MASS AND

825
00:30:23,440 --> 00:30:25,320
ACTIVITY, WE USE PET/CT AS I

826
00:30:25,320 --> 00:30:26,600
SHOWED YOU AND I'LL SHOW YOU

827
00:30:26,600 --> 00:30:28,720
SOME IMAGES IN OUR STUDIES,

828
00:30:28,720 --> 00:30:29,920
WE'RE DEVELOPING MRI IN

829
00:30:29,920 --> 00:30:30,520
COLLABORATION WITH COLLEAGUES

830
00:30:30,520 --> 00:30:32,760
HERE AT THE NIH, AND USING

831
00:30:32,760 --> 00:30:33,040
ULTRASOUND.

832
00:30:33,040 --> 00:30:35,760
ON THE OTHER SIDE, YOU NEED TO

833
00:30:35,760 --> 00:30:37,160
UNDERSTAND MECHANISM, AND WHILE

834
00:30:37,160 --> 00:30:39,720
ONE CAN USE CLINICAL TRIALS, ONE

835
00:30:39,720 --> 00:30:42,200
CAN GET MUCH MORE DETAILED AND

836
00:30:42,200 --> 00:30:43,440
WELL DESIGNED STUDIES USING

837
00:30:43,440 --> 00:30:45,640
HUMAN AND RODENT MODELS TO LOOK

838
00:30:45,640 --> 00:30:47,720
AT BIOINER JE TICS, THE HEAT

839
00:30:47,720 --> 00:30:53,640
BEING GENERATED, BIOINFORMATICS,

840
00:30:53,640 --> 00:30:54,960
AND INTERVENTIONAL THROUGH GENE

841
00:30:54,960 --> 00:30:55,480
EDITING AND REGULATION.

842
00:30:55,480 --> 00:30:57,960
THEN WE CAN GO FROM THE BED TO

843
00:30:57,960 --> 00:31:01,000
THE BENCH BACK TO BED AND DO

844
00:31:01,000 --> 00:31:03,280
THERAPEUTIC TRIALS WHERE YOU USE

845
00:31:03,280 --> 00:31:05,160
MILD COLD EXPOSURE AND IN

846
00:31:05,160 --> 00:31:06,760
PARTICULAR, BETA THREE

847
00:31:06,760 --> 00:31:08,160
ADRENERGIC RECEPTOR AGONISTS, IN

848
00:31:08,160 --> 00:31:10,320
PARTICULAR, MIRABEGRON, WHICH I

849
00:31:10,320 --> 00:31:10,960
WILL SHOW YOU.

850
00:31:10,960 --> 00:31:13,040
SO HOW DO YOU ACTIVATE BROWN

851
00:31:13,040 --> 00:31:15,320
FAT?

852
00:31:15,320 --> 00:31:16,600
COLD EXPOSURE IS WHAT'S COMMONLY

853
00:31:16,600 --> 00:31:16,880
USED.

854
00:31:16,880 --> 00:31:19,600
THIS IS ME TESTING OUT A SYSTEM

855
00:31:19,600 --> 00:31:21,000
BACK IN 2010.

856
00:31:21,000 --> 00:31:22,360
WHEN WE FIRST WANTED TO USE COLD

857
00:31:22,360 --> 00:31:23,680
EXPOSURE WE WEREN'T SURE BEST

858
00:31:23,680 --> 00:31:24,360
HOW TO DO IT.

859
00:31:24,360 --> 00:31:25,520
THANKS TO NUMEROUS CONVERSATIONS

860
00:31:25,520 --> 00:31:31,080
AND ASSISTANCE FROM MARTIN T

861
00:31:31,080 --> 00:31:33,200
TORRIANI AND GRINSPOON,

862
00:31:33,200 --> 00:31:35,440
COLLEAGUES AND COLLABORATORS, WE

863
00:31:35,440 --> 00:31:36,240
IDENTIFIED THIS VEST SYSTEM AND

864
00:31:36,240 --> 00:31:38,120
WE WERE ABLE TO INFUSE WATER

865
00:31:38,120 --> 00:31:38,840
THROUGH THESE TUBES HERE.

866
00:31:38,840 --> 00:31:40,560
YOU CAN SEE TUBES ON A VEST THAT

867
00:31:40,560 --> 00:31:42,600
I'M WEARING AND WE'RE ABLE TO

868
00:31:42,600 --> 00:31:43,800
INCREASE THE BROWN FAT

869
00:31:43,800 --> 00:31:46,400
ACTIVATION.

870
00:31:46,400 --> 00:31:48,280
WE MOVE TO A PHARMACOLOGICAL

871
00:31:48,280 --> 00:31:49,400
APPROACH, SO WHY DO THAT?

872
00:31:49,400 --> 00:31:51,240
FOR ONE THING, A PHARMACOLOGICAL

873
00:31:51,240 --> 00:31:53,800
APPROACH ALLOWS FOR POTENTIAL

874
00:31:53,800 --> 00:31:55,400
FOR MORE SPECIFIC TARGETING OF

875
00:31:55,400 --> 00:31:56,280
HUMAN BROWN FAT.

876
00:31:56,280 --> 00:32:00,800
AS I'LL GO INTO MORE DETAIL, THE

877
00:32:00,800 --> 00:32:01,440
BETA THREE ADRENERGIC REACCEPT

878
00:32:01,440 --> 00:32:05,680
PORE IS EX-TRESSED IN VERY FEW

879
00:32:05,680 --> 00:32:08,640
ORGANS BUT BROWN FAT IS ONE OF

880
00:32:08,640 --> 00:32:09,320
THEM.

881
00:32:09,320 --> 00:32:12,000
ANIMAL MODELS SHOW THEY ARE VERY

882
00:32:12,000 --> 00:32:13,720
EFFECTIVE IN METABOLIC HEALTH.

883
00:32:13,720 --> 00:32:14,560
THERE'S LIKELY TO BE GREATER

884
00:32:14,560 --> 00:32:15,680
ADHERENCE FROM A PATIENT

885
00:32:15,680 --> 00:32:16,480
POPULATION IF THEY HAVE TO TAKE

886
00:32:16,480 --> 00:32:19,680
A FEW PILLS RATHER THAN HAVING

887
00:32:19,680 --> 00:32:21,200
TO SIT IN THE COLD FOR TWO OR

888
00:32:21,200 --> 00:32:23,800
EVEN SIX HOURS A DAY.

889
00:32:23,800 --> 00:32:25,200
AND IN THE END, ACCOMMODATIONS

890
00:32:25,200 --> 00:32:27,120
OF APPROACHES MAY BE NECESSARY.

891
00:32:27,120 --> 00:32:29,640
THE FACT IS THAT COLD MAY BE

892
00:32:29,640 --> 00:32:31,480
HELPFUL WITH USING DRUGS OR

893
00:32:31,480 --> 00:32:34,080
MULTIPLE MEDICATIONS TOGETHER.

894
00:32:34,080 --> 00:32:36,680
SO I'M GOING TO TALK ABOUT THE

895
00:32:36,680 --> 00:32:38,440
BETA 3 ADRENERGIC RECEPTOR

896
00:32:38,440 --> 00:32:38,800
AGONISTS.

897
00:32:38,800 --> 00:32:40,280
THEY CAN BE USED WIDELY IN

898
00:32:40,280 --> 00:32:42,160
HUMANS AND THAT WASN'T TRUE

899
00:32:42,160 --> 00:32:42,720
UNTIL 2012.

900
00:32:42,720 --> 00:32:44,440
AND IT CAME FROM, AGAIN, A VERY

901
00:32:44,440 --> 00:32:46,400
DIFFERENT AREA OF MEDICINE.

902
00:32:46,400 --> 00:32:49,360
THIS TIME UROLOGY.

903
00:32:49,360 --> 00:32:51,080
TURNS OUT OVER 45 MILLION PEOPLE

904
00:32:51,080 --> 00:32:52,120
IN THE UNITED STATES ARE

905
00:32:52,120 --> 00:32:53,800
AFFECTED BY OVERACTIVE BLADDER,

906
00:32:53,800 --> 00:32:57,000
AND THAT'S COMPARED FOR EXAMPLE

907
00:32:57,000 --> 00:32:58,800
TO 26 MILLION WITH TYPE 1 AND

908
00:32:58,800 --> 00:33:00,040
TYPE 2 DIABETES COMBINED.

909
00:33:00,040 --> 00:33:03,040
NOW THERE ARE BETA 3 ADRENERGIC

910
00:33:03,040 --> 00:33:04,760
RECEPTORS IN THE URINARY

911
00:33:04,760 --> 00:33:05,240
BLADDER.

912
00:33:05,240 --> 00:33:06,880
ACTIVATION OF THESE RECEPTORS

913
00:33:06,880 --> 00:33:08,680
RELAXES THE BLADDER AND THEN

914
00:33:08,680 --> 00:33:10,200
ALLOWS TO HOLD MORE URINE AND SO

915
00:33:10,200 --> 00:33:11,360
SOMEONE DOESN'T HAVE TO RUN TO

916
00:33:11,360 --> 00:33:13,240
THE BATHROOM THAT FREQUENTLY.

917
00:33:13,240 --> 00:33:17,320
NOW THIS IS MEDICATION

918
00:33:17,320 --> 00:33:20,360
MIRABEGRON, A BETA THREE

919
00:33:20,360 --> 00:33:21,480
ADRENERGIC RECEPTOR AGONIST AND

920
00:33:21,480 --> 00:33:23,840
WAS APPROVED IN 2012 BY THE FDA

921
00:33:23,840 --> 00:33:25,600
FOR TREATMENT OF OVERACTIVE BLAH

922
00:33:25,600 --> 00:33:27,200
TER AT MAXIMUM DOSAGE OF

923
00:33:27,200 --> 00:33:27,720
50 MILLIGRAMS DAILY.

924
00:33:27,720 --> 00:33:30,200
AS I MENTIONED THERE ARE ALSO

925
00:33:30,200 --> 00:33:31,440
BETA THREE ADRENERGIC RECEPTORS

926
00:33:31,440 --> 00:33:33,040
IN BOTH HUMAN WHITE AND BROWN

927
00:33:33,040 --> 00:33:33,280
FAT.

928
00:33:33,280 --> 00:33:34,920
SO WE WANTED TO DO A PROOF OF

929
00:33:34,920 --> 00:33:36,240
CONCEPT STUDY DESIGN AND THIS

930
00:33:36,240 --> 00:33:39,960
WAS LED BY LAUREN WEINER,

931
00:33:39,960 --> 00:33:41,080
DR. WEINER NOW, AND IN THIS

932
00:33:41,080 --> 00:33:43,080
STUDY, WE WANTED TO SEE THE

933
00:33:43,080 --> 00:33:48,440
EFFECTS OF MIRABEGRON ON 12

934
00:33:48,440 --> 00:33:49,080
YOUNG, LEAN, HEALTHY MEN.

935
00:33:49,080 --> 00:33:51,920
WE WANTED TO SEE IF IT COULD

936
00:33:51,920 --> 00:33:54,160
ACTIVATE THE BROWN FAT AND

937
00:33:54,160 --> 00:33:55,080
INCREASE THERMOGENESIS.

938
00:33:55,080 --> 00:33:57,680
SO WE CONDUCTED THE STUDY WITH

939
00:33:57,680 --> 00:33:59,040
PLACEBO AS THE NEGATIVE CONTROL,

940
00:33:59,040 --> 00:34:00,400
MILD COLD AS THE POSITIVE

941
00:34:00,400 --> 00:34:03,000
CONTROL, AND BY TESTING OUT THIS

942
00:34:03,000 --> 00:34:04,240
VEST SYSTEM THAT I SHOWED YOU

943
00:34:04,240 --> 00:34:04,760
PREVIOUSLY.

944
00:34:04,760 --> 00:34:08,360
AND THEN WE GAVE MIRABEGRON AT

945
00:34:08,360 --> 00:34:10,480
200 MILLIGRAMS, A ONE-TIME DOES.

946
00:34:10,480 --> 00:34:12,280
WE CHOSE THAT DOSE BECAUSE WE

947
00:34:12,280 --> 00:34:15,280
DIDN'T WANT A FALSE NEGATIVE

948
00:34:15,280 --> 00:34:18,240
SIGNAL SO WE CHOSE THE HIGHEST

949
00:34:18,240 --> 00:34:22,720
DOSE HIGHEST IN CLINICAL TRIALS,

950
00:34:22,720 --> 00:34:23,920
SAFE IN MEN BUT NOT IN WOMEN SO

951
00:34:23,920 --> 00:34:25,520
WE HAD TO STUDY MEN FIRST.

952
00:34:25,520 --> 00:34:27,000
WE EVENTUALLY STUDIED WOMEN AS

953
00:34:27,000 --> 00:34:28,040
I'LL SHOW YOU LATER.

954
00:34:28,040 --> 00:34:30,760
IN THIS STUDY WE MONITOR VITAL

955
00:34:30,760 --> 00:34:33,360
SIGNS, ENERGY EXPENDITURE AND

956
00:34:33,360 --> 00:34:35,800
MEASURED BROWN FAT METABOLIC

957
00:34:35,800 --> 00:34:36,360
ACTIVITY.

958
00:34:36,360 --> 00:34:37,640
THE FIRST THING WE IDENTIFIED

959
00:34:37,640 --> 00:34:39,200
WAS THAT THERE WAS AN INCREASE

960
00:34:39,200 --> 00:34:42,240
IN ENERGY EXPENDITURE, 200 KILL

961
00:34:42,240 --> 00:34:44,640
CALORIES PER DAY, THE HIGHEST

962
00:34:44,640 --> 00:34:48,640
WITH THE MIRABEGRON IN BLACK,

963
00:34:48,640 --> 00:34:50,600
BOTH VERY EFFECTIVE AS WE

964
00:34:50,600 --> 00:34:51,360
EXPECTED.

965
00:34:51,360 --> 00:34:52,800
ALSO AN INCREASE IN SYSTOLIC

966
00:34:52,800 --> 00:34:55,960
BLOOD PRESSURE IN BOTH THE

967
00:34:55,960 --> 00:34:57,120
MIRABEGRON IN BLACK AND COLD

968
00:34:57,120 --> 00:34:58,960
EXPOSURE IN GREY THAT WE KNEW

969
00:34:58,960 --> 00:35:00,680
WOULD HAPPEN AND THAT'S WHY WE

970
00:35:00,680 --> 00:35:02,840
CANNOT USE 100 OR 200 FOR ANY

971
00:35:02,840 --> 00:35:03,720
KIND OF CHRONIC TREATMENT BUT

972
00:35:03,720 --> 00:35:05,800
FOR THIS KIND OF EXPERIMENT IT'S

973
00:35:05,800 --> 00:35:07,080
USEFUL.

974
00:35:07,080 --> 00:35:09,920
DIASTOLIC BLOOD PRESSURE DIDN'T

975
00:35:09,920 --> 00:35:12,280
CHANGE MUCH BUT HEART RATE WENT

976
00:35:12,280 --> 00:35:16,560
UP 13 BEATS PER MINUTE WITH MIR

977
00:35:16,560 --> 00:35:17,040
ABEGRON.

978
00:35:17,040 --> 00:35:18,920
WHEN COLD EXPOSURE IS USED IT

979
00:35:18,920 --> 00:35:19,680
CAUSES INCREASE IN BLOOD

980
00:35:19,680 --> 00:35:21,960
PRESSURE AND THE HEART RATE

981
00:35:21,960 --> 00:35:23,560
RESPONDS BY GOING DOWN TO REDUCE

982
00:35:23,560 --> 00:35:24,320
THE OVERALL BLOOD PRESSURE IN

983
00:35:24,320 --> 00:35:26,920
THE BODY.

984
00:35:26,920 --> 00:35:29,120
MIRABEGRON OVERRIDES THE SYSTEM

985
00:35:29,120 --> 00:35:30,520
AND CAUSES INCREASE IN BLOOD

986
00:35:30,520 --> 00:35:31,080
PRESSURE AND HEART RATE.

987
00:35:31,080 --> 00:35:31,840
SO WHAT HAPPENED TO THE BROWN

988
00:35:31,840 --> 00:35:32,240
FAT?

989
00:35:32,240 --> 00:35:34,240
WELL, THIS IS A PET IMAGE

990
00:35:34,240 --> 00:35:35,360
SHOWING WHERE THE GLUCOSE IS

991
00:35:35,360 --> 00:35:37,000
GOING INTO A 21-YEAR-OLD MAN,

992
00:35:37,000 --> 00:35:38,560
IT'S GOING INTO THE HEART HERE.

993
00:35:38,560 --> 00:35:40,840
IT'S GOING INTO HIS BRAIN HERE.

994
00:35:40,840 --> 00:35:42,400
IT'S BEING FILTERED BY THE

995
00:35:42,400 --> 00:35:43,680
KIDNEYS OVER HERE, BUT NOTHING

996
00:35:43,680 --> 00:35:44,800
ELSE IN THE REGION WHERE WE

997
00:35:44,800 --> 00:35:46,920
TYPICALLY SEE BROWN FAT.

998
00:35:46,920 --> 00:35:48,800
WITH COLD EXPOSURE, THERE WAS A

999
00:35:48,800 --> 00:35:50,080
MASSIVE INCREASE IN GLUCOSE

1000
00:35:50,080 --> 00:35:51,160
UPTAKE IN THE BROWN FAT AS YOU

1001
00:35:51,160 --> 00:35:53,400
CAN SEE IN THE SHOULDERS, DOWN

1002
00:35:53,400 --> 00:35:56,400
THE SPINE, AND INTO THE KIDNEY

1003
00:35:56,400 --> 00:35:57,120
REGION.

1004
00:35:57,120 --> 00:36:05,160
IN ADDITION, MIR ABEG RON WAS

1005
00:36:05,160 --> 00:36:06,800
VERY EFFECTIVE.

1006
00:36:06,800 --> 00:36:09,320
ENERGY EXPENDITURE INCREASES IN

1007
00:36:09,320 --> 00:36:10,840
THERMOGENESIS BY THE BROWN FAT

1008
00:36:10,840 --> 00:36:14,800
IN THE SHOULDERS, SPINE, AND THE

1009
00:36:14,800 --> 00:36:18,360
KIDNEYS.

1010
00:36:18,360 --> 00:36:20,760
WE FOUND BROWN FAT NOT SEEN ON

1011
00:36:20,760 --> 00:36:22,040
AUTOPSY OR OTHER KIND OF STUDY,

1012
00:36:22,040 --> 00:36:23,360
SO DONE IN REALTIME IN HEALTHY

1013
00:36:23,360 --> 00:36:27,960
PATIENTS IS VERY HELPFUL.

1014
00:36:27,960 --> 00:36:30,640
SO WHAT WILL HAPPEN AFTER LONG

1015
00:36:30,640 --> 00:36:32,120
TERM THERAPY WITH MIRABEGRON?

1016
00:36:32,120 --> 00:36:33,120
WELL, I GOT AS FAR AS WE COULD

1017
00:36:33,120 --> 00:36:34,560
IN THE STUDIES WE WERE ABLE TO

1018
00:36:34,560 --> 00:36:36,360
CONDUCT IN BOSTON SO I MOVED TO

1019
00:36:36,360 --> 00:36:37,640
THE NIH CLINICAL CENTER AND WAS

1020
00:36:37,640 --> 00:36:39,480
ABLE TO TAKE ADVANTAGE OF THE

1021
00:36:39,480 --> 00:36:40,960
TEAM AND THE NIH METABOLIC

1022
00:36:40,960 --> 00:36:43,080
CLINICAL RESEARCH UNIT OF THE

1023
00:36:43,080 --> 00:36:45,600
MCRU, AND IN PARTICULAR,

1024
00:36:45,600 --> 00:36:49,360
COLLABORATIONS WITH CONGRESS KO,

1025
00:36:49,360 --> 00:36:51,760
WHO RUNS THE HUMAN ENERGY AND

1026
00:36:51,760 --> 00:36:52,720
BODY WEIGHT REGULATION CORE IN

1027
00:36:52,720 --> 00:36:54,960
THE BUILDING 10 CLINICAL CENTER.

1028
00:36:54,960 --> 00:36:59,160
THE METABOLIC RESEARCH UNIT ON Y

1029
00:36:59,160 --> 00:37:01,040
SPECIAL PLACE, UNLIKE ALMOST ANY

1030
00:37:01,040 --> 00:37:02,000
OTHER PLACE IN THE COUNTRY.

1031
00:37:02,000 --> 00:37:03,120
THERE ARE EIGHT PRIVATE

1032
00:37:03,120 --> 00:37:05,120
INPATIENT RESEARCH BEDS, AND

1033
00:37:05,120 --> 00:37:06,640
THESE ROOMS ARE DESIGNED FOR

1034
00:37:06,640 --> 00:37:07,160
METABOLIC STUDY.

1035
00:37:07,160 --> 00:37:09,120
SO YOU CAN SEE HERE OUR TYPICAL

1036
00:37:09,120 --> 00:37:09,800
ROOM.

1037
00:37:09,800 --> 00:37:11,320
HERE'S A BED AND HERE ARE THE

1038
00:37:11,320 --> 00:37:12,680
CHAIRS, AND YOU'LL NOTICE THAT

1039
00:37:12,680 --> 00:37:13,760
THEY'RE LARGER THAN A TYPICAL

1040
00:37:13,760 --> 00:37:15,880
BED OR CHAIR AND THAT WAY WE CAN

1041
00:37:15,880 --> 00:37:17,400
ACCOMMODATE PEOPLE OF A VARIETY

1042
00:37:17,400 --> 00:37:20,920
OF SIZES AND WEIGHTS.

1043
00:37:20,920 --> 00:37:23,800
WE COULD ALSO MEASURE ENERGY

1044
00:37:23,800 --> 00:37:25,680
EXPENDITURE USING A PROCESS

1045
00:37:25,680 --> 00:37:28,880
CALLED INDIRECT CALORIMETRY,

1046
00:37:28,880 --> 00:37:30,240
TESTING OUT A SYSTEM HERE, AND

1047
00:37:30,240 --> 00:37:31,920
IT'S DONE SHORT TERM, YOU CAN DO

1048
00:37:31,920 --> 00:37:33,480
BREATH TO BREATH OR MINUTE TO

1049
00:37:33,480 --> 00:37:35,360
MINUTE IN THE METABOLIC UNIT.

1050
00:37:35,360 --> 00:37:39,080
THERE'S ALSO A WHOLE ROOM

1051
00:37:39,080 --> 00:37:39,920
CALORIMETER, I'LL SHOW YOU HOW

1052
00:37:39,920 --> 00:37:41,120
THAT WORKS IN A MINUTE.

1053
00:37:41,120 --> 00:37:42,360
THAT'S ALSO MEDIUM TERM MINUTES

1054
00:37:42,360 --> 00:37:43,600
TO HOURS AND THEN THERE'S A

1055
00:37:43,600 --> 00:37:45,680
PROCESS USING DOUBLY LABELED

1056
00:37:45,680 --> 00:37:47,560
WATER THAT PEOPLE DRINK, AND

1057
00:37:47,560 --> 00:37:49,000
THAT'S HOW ONE CAN MEASURE LONG

1058
00:37:49,000 --> 00:37:52,000
TERM ENERGY EXPENDITURE IN FREE

1059
00:37:52,000 --> 00:37:52,400
LIVING PEOPLE.

1060
00:37:52,400 --> 00:37:54,800
I'M NOT GOING TO TALK ABOUT THIS

1061
00:37:54,800 --> 00:37:56,000
TODAY.

1062
00:37:56,000 --> 00:37:57,160
IF YOU'RE GOING TO BE ABLE TO

1063
00:37:57,160 --> 00:37:58,000
STUDY METABOLIC CHANGES, YOU

1064
00:37:58,000 --> 00:37:59,960
NEED TO HAVE A GREAT KITCHEN AND

1065
00:37:59,960 --> 00:38:00,440
NUTRITIONAL UNIT.

1066
00:38:00,440 --> 00:38:02,680
SHOWN HERE IS ONE IMAGE OF THE

1067
00:38:02,680 --> 00:38:05,040
NUTRITIONAL UNIT AT THE CLINICAL

1068
00:38:05,040 --> 00:38:05,960
CENTER, AND DR. HALL WILL TALK

1069
00:38:05,960 --> 00:38:08,240
MORE ABOUT THAT HOW THAT HAS

1070
00:38:08,240 --> 00:38:09,080
SUPPORTED HIS STUDIES.

1071
00:38:09,080 --> 00:38:12,160
AND SHOWN HERE, ONE CAN MEASURE

1072
00:38:12,160 --> 00:38:14,640
ENERGY EXPENDITURE USING AN

1073
00:38:14,640 --> 00:38:16,040
EXERCISE BIKE, OR RESTING ENERGY

1074
00:38:16,040 --> 00:38:17,160
EXPENDITURE HERE.

1075
00:38:17,160 --> 00:38:18,360
AND AGAIN AS I MENTIONED, THIS

1076
00:38:18,360 --> 00:38:20,360
IS DONE FOR 30 MINUTES ROUGHLY,

1077
00:38:20,360 --> 00:38:24,080
AND IT'S DONE IN AWAKE, FASTED

1078
00:38:24,080 --> 00:38:24,960
VOLUNTEERS, EITHER LYING DOWN

1079
00:38:24,960 --> 00:38:27,920
AND RESTING OR THEN EXERCISING,

1080
00:38:27,920 --> 00:38:30,120
AND THE ADVANTAGES OF THIS

1081
00:38:30,120 --> 00:38:31,360
SYSTEM IS THAT THEY'RE ACCURATE

1082
00:38:31,360 --> 00:38:32,160
MEASUREMENTS WHEN BEST PRACTICES

1083
00:38:32,160 --> 00:38:33,880
ARE FOLLOWED AND IT'S A

1084
00:38:33,880 --> 00:38:35,000
RELATIVELY INEXPENSIVE AND

1085
00:38:35,000 --> 00:38:38,480
SOMEWHAT PORTABLE SYSTEM.

1086
00:38:38,480 --> 00:38:39,920
HOWEVER, IF YOU WANT TO

1087
00:38:39,920 --> 00:38:41,760
UNDERSTAND THE ROLES OF THE

1088
00:38:41,760 --> 00:38:43,360
DIFFERENT PARTS OF THE BODY, YOU

1089
00:38:43,360 --> 00:38:45,040
NEED TO MEASURE BODY

1090
00:38:45,040 --> 00:38:45,320
COMPOSITION.

1091
00:38:45,320 --> 00:38:47,080
AND THE BEST WAY WE FIND TO DO

1092
00:38:47,080 --> 00:38:49,200
IT IS IN OUR BODY COMPOSITION

1093
00:38:49,200 --> 00:38:50,920
LABORATORY ON 7 SOUTHWEST SOUTH,

1094
00:38:50,920 --> 00:38:52,480
AND THAT'S USING SOMETHING

1095
00:38:52,480 --> 00:38:59,280
CALLED DUAL ENERGY X-RAY

1096
00:38:59,280 --> 00:39:00,920
ABSORPTIOMETRY OR DXA, IT TAITS

1097
00:39:00,920 --> 00:39:02,600
ABOUT 10 TO 12 MINUTES AND

1098
00:39:02,600 --> 00:39:03,480
MEASURED THREE DIFFERENT

1099
00:39:03,480 --> 00:39:04,640
COMPARTMENTS OF THE BODY.

1100
00:39:04,640 --> 00:39:06,440
FAT MASS, LEAN MASS, AND THE

1101
00:39:06,440 --> 00:39:07,640
BONE MINERAL CONTENT.

1102
00:39:07,640 --> 00:39:09,960
THIS IS HIGHLY REPRODUCIBLE,

1103
00:39:09,960 --> 00:39:11,840
PLUS OR MINUS 1%.

1104
00:39:11,840 --> 00:39:16,080
IT PROVIDES GOOD REGIONAL BODY

1105
00:39:16,080 --> 00:39:17,760
COMPOSITION INFORMATION, AROUND

1106
00:39:17,760 --> 00:39:21,160
AND FORTUNATELY IT HAS A VERY

1107
00:39:21,160 --> 00:39:23,720
SMALL AMOUNT OF RADIATION

1108
00:39:23,720 --> 00:39:24,480
EXPOSURE.

1109
00:39:24,480 --> 00:39:26,960
ROUGHLY THE SAME AMOUNT OF ONE

1110
00:39:26,960 --> 00:39:28,040
DAY'S SUNLIGHT EXPOSURE OR ABOUT

1111
00:39:28,040 --> 00:39:30,360
1% OF WHAT YOU'D HAVE IN A CHESS

1112
00:39:30,360 --> 00:39:33,280
EXRAI.

1113
00:39:33,280 --> 00:39:34,600
 CHEST

1114
00:39:34,600 --> 00:39:34,800
X-RAY.

1115
00:39:34,800 --> 00:39:38,040
THE ROOM CALORIMETER IS WHERE

1116
00:39:38,040 --> 00:39:39,680
YOU CAN DO THE MOST STUDY, AND

1117
00:39:39,680 --> 00:39:41,440
I'LL SHOW YOU THE DESIGN AND

1118
00:39:41,440 --> 00:39:42,320
ADVANTAGES OF IT.

1119
00:39:42,320 --> 00:39:44,120
A VOLUNTEER PATIENT CAN BE

1120
00:39:44,120 --> 00:39:45,320
SITTING IN THIS ROOM, THEY'LL BE

1121
00:39:45,320 --> 00:39:48,480
TAKING IN OXYGEN, GIVING OFF

1122
00:39:48,480 --> 00:39:50,880
CARBON DIOXIDE, THE AIR MIXING

1123
00:39:50,880 --> 00:39:52,240
FAN SENDS AIR TO THE TUBES AND

1124
00:39:52,240 --> 00:39:53,120
EFFICIENTLY THE AIR IS THEN

1125
00:39:53,120 --> 00:39:57,040
GOING THROUGH A PUMP AND THEN

1126
00:39:57,040 --> 00:39:59,360
CARBON DIOXIDE AND OXYGEN

1127
00:39:59,360 --> 00:40:00,440
ANALYZERS TELL YOU HOW MUCH OF

1128
00:40:00,440 --> 00:40:01,920
EACH OF THESE GASES ARE BEING

1129
00:40:01,920 --> 00:40:03,600
CONSUMED AND PRODUCED BY THE

1130
00:40:03,600 --> 00:40:08,400
BODY.

1131
00:40:08,400 --> 00:40:10,960
IN ADDITION TO THE CART, WHEN

1132
00:40:10,960 --> 00:40:12,640
RUN WELL BY OUR TEAM HERE IS

1133
00:40:12,640 --> 00:40:14,160
HIGHLY REPRODUCIBLE AND CAN GIVE

1134
00:40:14,160 --> 00:40:15,880
AN ACCURATE MEASUREMENT OF

1135
00:40:15,880 --> 00:40:17,880
ENERGY EXPENDITURE SITTING,

1136
00:40:17,880 --> 00:40:19,080
EXERCISING OR SLEEPING EVEN.

1137
00:40:19,080 --> 00:40:20,480
IT ALLOWS MORE FLEXIBILITY IN

1138
00:40:20,480 --> 00:40:22,560
TERMS OF WHAT PEOPLE DO THAN THE

1139
00:40:22,560 --> 00:40:23,080
METABOLIC CARTS.

1140
00:40:23,080 --> 00:40:24,920
AND IT'S APPROPRIATE TO MEASURE

1141
00:40:24,920 --> 00:40:26,160
ADAPTIVE THERMOGENESIS, IN OTHER

1142
00:40:26,160 --> 00:40:27,720
WORDS, HOW THE BODY RESPONDS IN

1143
00:40:27,720 --> 00:40:30,320
TERMS OF HEAT GENERATION WHEN

1144
00:40:30,320 --> 00:40:32,480
THERE ARE CHANGES IN DIET,

1145
00:40:32,480 --> 00:40:32,960
AMBIENT TEMPERATURE.

1146
00:40:32,960 --> 00:40:35,400
THESE ROOMS CAN BE TAKEN DOWN TO

1147
00:40:35,400 --> 00:40:37,360
20 DEGREES CELSIUS OR 60 DEGREES

1148
00:40:37,360 --> 00:40:38,200
FAHRENHEIT, AND HOW PEOPLE

1149
00:40:38,200 --> 00:40:40,160
RESPOND TO MEDICINES AND OTHER

1150
00:40:40,160 --> 00:40:41,000
STRUCTURED ACTIVITIES.

1151
00:40:41,000 --> 00:40:42,440
WHAT DOES THIS ROOM LOOK LIKE?

1152
00:40:42,440 --> 00:40:43,480
THIS IS HOW YOU WALK IN.

1153
00:40:43,480 --> 00:40:44,720
THIS IS THE WELCOME VIEW.

1154
00:40:44,720 --> 00:40:46,640
HERE'S A BED, HERE'S A WINDOW TO

1155
00:40:46,640 --> 00:40:49,440
THE OUTSIDE, A TAPESTRY, AND

1156
00:40:49,440 --> 00:40:51,080
THEN A WORK STATION ONE CAN WORK

1157
00:40:51,080 --> 00:40:51,240
AT.

1158
00:40:51,240 --> 00:40:52,800
HONESTLY THIS IS A LOT NICER

1159
00:40:52,800 --> 00:40:56,080
THAN MY DORM ROOM WHEN I WAS IN

1160
00:40:56,080 --> 00:40:56,280
COLLEGE.

1161
00:40:56,280 --> 00:40:57,320
WHAT IT LOOKS LIKE IN TERMS OF

1162
00:40:57,320 --> 00:40:58,520
THE INTERFACE WITH THE CARE

1163
00:40:58,520 --> 00:41:01,520
TEAM, CAN  YOU CAN SEE COMPUTERM

1164
00:41:01,520 --> 00:41:02,600
BEFORE, THIS IS WHERE ONE CAN

1165
00:41:02,600 --> 00:41:03,920
GET FOOD BEING BROUGHT IN

1166
00:41:03,920 --> 00:41:05,160
THROUGH THESE WINDOWS HERE, THIS

1167
00:41:05,160 --> 00:41:06,480
IS THE DOOR TO THE OUTSIDE, AND

1168
00:41:06,480 --> 00:41:09,160
THEN IF ONE WANTS TO HAVE

1169
00:41:09,160 --> 00:41:11,280
SOMETHING INFUSED, FOR EXAMPLE

1170
00:41:11,280 --> 00:41:14,040
THE TRACER FOR THE PET/CT

1171
00:41:14,040 --> 00:41:15,200
STUDIES, ONE CAN STICK ONE'S ARM

1172
00:41:15,200 --> 00:41:16,560
THROUGH HERE AND MAINTAIN THE

1173
00:41:16,560 --> 00:41:18,600
ABILITY TO MEASURE THE OXYGEN

1174
00:41:18,600 --> 00:41:19,200
CARBON DIOXIDE.

1175
00:41:19,200 --> 00:41:22,480
ON THE OW SIDE  OUTSIDE OF THESS

1176
00:41:22,480 --> 00:41:24,200
IS WHERE THE PRECISION EQUIPMENT

1177
00:41:24,200 --> 00:41:25,680
IS KEPT, JUST SHOWING WHAT IT

1178
00:41:25,680 --> 00:41:26,880
LOOKS LIKE IN THE OVERALL SENSE,

1179
00:41:26,880 --> 00:41:28,600
AND THEN WE HAVE HERE THE

1180
00:41:28,600 --> 00:41:30,400
MEASUREMENT, THE TEMPERATURE,

1181
00:41:30,400 --> 00:41:32,520
THE CONSUMPTION OF OXYGEN,

1182
00:41:32,520 --> 00:41:33,360
RELATIVE HUMIDITY AND ALL THESE

1183
00:41:33,360 --> 00:41:34,120
THINGS BEING TESTED AT THE SAME

1184
00:41:34,120 --> 00:41:36,360
TIME.

1185
00:41:36,360 --> 00:41:39,680
AND SO WE HAVE THE TOOLS, WE

1186
00:41:39,680 --> 00:41:41,400
HAVE THE TALENT.

1187
00:41:41,400 --> 00:41:42,640
LET'S CONDUCT SOME CLINICAL

1188
00:41:42,640 --> 00:41:44,040
TRIALS.

1189
00:41:44,040 --> 00:41:47,200
SO ONE OF THE KEY ONES IS

1190
00:41:47,200 --> 00:41:47,920
CHRONIC MIRABEGRON TREATMENT.

1191
00:41:47,920 --> 00:41:49,800
WE SHOWED YOU WHAT HAPPENS

1192
00:41:49,800 --> 00:41:50,720
ACUTELY, A LOT OF EXCITING

1193
00:41:50,720 --> 00:41:50,960
THINGS.

1194
00:41:50,960 --> 00:41:58,760
A STUDY LED BY EELY NA OMARA,

1195
00:41:58,760 --> 00:41:59,760
STARTING RESIDENCY IN TWO

1196
00:41:59,760 --> 00:42:00,000
MONTHS.

1197
00:42:00,000 --> 00:42:01,760
IN THIS COHORT OUR PRIMARY END

1198
00:42:01,760 --> 00:42:03,320
POINT IS THE CHANGE IN

1199
00:42:03,320 --> 00:42:05,320
DETECTABLE BROWN FAT METABOLIC

1200
00:42:05,320 --> 00:42:07,240
ACTIVITY ASSOCIATED WITH THE

1201
00:42:07,240 --> 00:42:09,680
DAILY DOSE OF MIRABEGRON OVER A

1202
00:42:09,680 --> 00:42:10,120
FOUR-WEEK PERIOD.

1203
00:42:10,120 --> 00:42:11,960
WE STUDIED 14 WOMEN THIS TIME

1204
00:42:11,960 --> 00:42:14,800
FOR FOUR WEEKS AS I MENTIONED,

1205
00:42:14,800 --> 00:42:15,560
100 MILLIGRAMS OF MIRABEGRON,

1206
00:42:15,560 --> 00:42:17,560
AND THEN WE USED THE

1207
00:42:17,560 --> 00:42:19,440
SOPHISTICATED TESTING EQUIPMENT

1208
00:42:19,440 --> 00:42:21,880
IN THE MCRU TO FIND OUT HOW THEY

1209
00:42:21,880 --> 00:42:24,400
RESPONDED ON BOTH THE INITIATION

1210
00:42:24,400 --> 00:42:27,840
AND AT COMPLETION.

1211
00:42:27,840 --> 00:42:29,840
DAY ZERO-1 AND DAY 27-28.

1212
00:42:29,840 --> 00:42:31,160
YOU CAN SEE HERE WE DID A

1213
00:42:31,160 --> 00:42:35,760
FREQUENTLY SAMPLED INTRAVENOUS

1214
00:42:35,760 --> 00:42:39,880
GLUCOSE TOLERANCE TEST, DID A

1215
00:42:39,880 --> 00:42:43,320
LIVER SCAN, EXERCISE TOLERANCE

1216
00:42:43,320 --> 00:42:46,000
TEST, BODY COMPOSITION WITH DXA,

1217
00:42:46,000 --> 00:42:47,480
THEY SPENT THE NIGHT IN THE

1218
00:42:47,480 --> 00:42:48,440
METABOLIC SUITE SO WE COULD

1219
00:42:48,440 --> 00:42:50,440
STUDY SLEEPING ENERGY

1220
00:42:50,440 --> 00:42:52,240
EXPENDITURE, WE DREW BLOOD, THEN

1221
00:42:52,240 --> 00:42:54,960
GAVE THE VOLUNTEERS MIRABEGRON,

1222
00:42:54,960 --> 00:42:57,480
DREW BLOOD AGAIN FIVE HOURS

1223
00:42:57,480 --> 00:42:59,840
LATER, GAVE FDG FOR THE PET/CT

1224
00:42:59,840 --> 00:43:01,440
STUDY WHICH WE DID AFTERWARD,

1225
00:43:01,440 --> 00:43:03,160
AND THEN THE VOLUNTEERS GOT

1226
00:43:03,160 --> 00:43:03,840
LUNCH.

1227
00:43:03,840 --> 00:43:04,640
WHAT DID WE FIND?

1228
00:43:04,640 --> 00:43:07,480
SO THIS IS DAY ONE, THIS IS DAY

1229
00:43:07,480 --> 00:43:09,320
28, THESE ARE 14 WOMEN, AND YOU

1230
00:43:09,320 --> 00:43:14,920
CAN SEE HERE BASED ON ALL THESE

1231
00:43:14,920 --> 00:43:17,400
OTHER ANTHROMETRIC MEASURES OF

1232
00:43:17,400 --> 00:43:18,960
THE BODY, THE ONLY THING THAT

1233
00:43:18,960 --> 00:43:20,320
MATTERED, JUST THE RESTING HEART

1234
00:43:20,320 --> 00:43:20,760
RATE.

1235
00:43:20,760 --> 00:43:21,880
AND THAT'S EXPECTED.

1236
00:43:21,880 --> 00:43:24,800
IT WENT UP BY 10 BEATS PER

1237
00:43:24,800 --> 00:43:25,040
MINUTE.

1238
00:43:25,040 --> 00:43:26,280
HOWEVER, AT MAXIMUM EXERCISE

1239
00:43:26,280 --> 00:43:27,520
THERE'S NO DIFFERENCE IN PULSE,

1240
00:43:27,520 --> 00:43:28,840
MEANING THAT MIRABEGRON LOWERED

1241
00:43:28,840 --> 00:43:30,320
THE FLOOR BUT DIDN'T HAVE ANY

1242
00:43:30,320 --> 00:43:32,600
OTHER EFFECTS.

1243
00:43:32,600 --> 00:43:35,040
I'M SORRY, RAISE THE THE FLOOR.

1244
00:43:35,040 --> 00:43:36,640
NOW, WHAT DID MIRABEGRON DO TO

1245
00:43:36,640 --> 00:43:38,120
BROWN FAT METABOLIC ACTIVITY AND

1246
00:43:38,120 --> 00:43:38,960
VOLUME?

1247
00:43:38,960 --> 00:43:41,160
SHOWN HERE IS A PET IMAGE OF ONE

1248
00:43:41,160 --> 00:43:43,200
OF THE VOLUNTEERS ON DAY ONE,

1249
00:43:43,200 --> 00:43:46,800
THE BLACK HERE, THE SPECKLED

1250
00:43:46,800 --> 00:43:48,200
AREA THAT'S PRETTY SPARSE IS HER

1251
00:43:48,200 --> 00:43:49,720
BROWN FAT, AND THEN AFTER 28

1252
00:43:49,720 --> 00:43:53,760
DAYS OF TREATMENT, YOU CAN SEE

1253
00:43:53,760 --> 00:43:55,960
ON THIS GREEN ARROW HERE, A

1254
00:43:55,960 --> 00:43:58,160
PROFOUND INCREASE IN GLUCOSE

1255
00:43:58,160 --> 00:43:59,200
UPTAKE, A VERY LARGE INCREASE IN

1256
00:43:59,200 --> 00:44:00,600
BROWN FAT MASS AND VOLUME.

1257
00:44:00,600 --> 00:44:02,160
NOT JUST IN THIS VOLUNTEER BUT

1258
00:44:02,160 --> 00:44:04,000
AMONG THE 14 PEOPLE STUDIED,

1259
00:44:04,000 --> 00:44:05,760
THERE WAS A VERY LARGE INCREASE

1260
00:44:05,760 --> 00:44:09,560
IN BROWN FAT METABOLIC ACTIVITY,

1261
00:44:09,560 --> 00:44:11,320
AND THERE WAS AN INCREASE IN THE

1262
00:44:11,320 --> 00:44:14,880
MAXIMUM BROWN FAT ACTIVITY TOO.

1263
00:44:14,880 --> 00:44:18,240
OUR PRIMARY END POINT WAS

1264
00:44:18,240 --> 00:44:21,160
REACHED, CHRONIC MIRABEGRON

1265
00:44:21,160 --> 00:44:21,880
100 MILLIMETERS WAS VERY

1266
00:44:21,880 --> 00:44:22,760
EFFECTIVE.

1267
00:44:22,760 --> 00:44:23,400
THAT'S NOT ALL WHAT MIRABEGRON

1268
00:44:23,400 --> 00:44:23,600
DID.

1269
00:44:23,600 --> 00:44:25,160
THIS IS WHERE WE DEPART FROM

1270
00:44:25,160 --> 00:44:26,280
BROWN FAT SPECIFICALLY TO OTHER

1271
00:44:26,280 --> 00:44:28,360
ORGANS IN THE BODY.

1272
00:44:28,360 --> 00:44:29,200
CHRONIC MIRABEGRON TREATMENT

1273
00:44:29,200 --> 00:44:30,800
RAISED THE HDL CHOLESTEROL.

1274
00:44:30,800 --> 00:44:33,600
THAT'S THE GOOD CHOLESTEROL, BY

1275
00:44:33,600 --> 00:44:33,760
8%.

1276
00:44:33,760 --> 00:44:35,960
IT ALSO INCREASED GIP.

1277
00:44:35,960 --> 00:44:37,880
THIS IS A HORMONE THAT INCREASES

1278
00:44:37,880 --> 00:44:38,640
INSULIN SENSITIVITY.

1279
00:44:38,640 --> 00:44:46,480
THAT INCREASED BY 30%.

1280
00:44:46,480 --> 00:44:48,280
ADIPONECTIN WENT UP BY 35%.

1281
00:44:48,280 --> 00:44:49,760
AND THE CIRCULATING LEVEL OF

1282
00:44:49,760 --> 00:44:52,000
BILE ACIDS IN THE BLOOD WENT UP

1283
00:44:52,000 --> 00:44:53,760
BY NEARLY 50%.

1284
00:44:53,760 --> 00:44:54,800
AND THAT'S IMPORTANT BECAUSE

1285
00:44:54,800 --> 00:44:56,760
BILE ACIDS, THEY'RE NOT JUST

1286
00:44:56,760 --> 00:44:59,360
SURFACTANTS THAT HELP ABSORB

1287
00:44:59,360 --> 00:45:01,480
DIETARY LIPIDS AND CHOLESTEROL,

1288
00:45:01,480 --> 00:45:03,080
THEY BIND TO HORMONE RECEPTORS

1289
00:45:03,080 --> 00:45:04,000
IN THE LIVER AND OTHER PLACES

1290
00:45:04,000 --> 00:45:08,080
AND CAUSE CHANGES IN GLUCOSE

1291
00:45:08,080 --> 00:45:09,200
HOMEOSTASIS, LIPOPROTEIN SUCH AS

1292
00:45:09,200 --> 00:45:12,240
THE GOOD CHOLESTEROL, BILE ACID

1293
00:45:12,240 --> 00:45:15,560
METABOLISM ITSELF, BILE ACIDS

1294
00:45:15,560 --> 00:45:17,840
MAY BE CARDIOPROTECTIVE, HAVE

1295
00:45:17,840 --> 00:45:24,120
IMPACTS ON THE GI, THE BRAIN,

1296
00:45:24,120 --> 00:45:26,080
SKM, BAT AND IMMUNE SYSTEM.

1297
00:45:26,080 --> 00:45:27,600
THESE CHANGES ALONE ARE ENOUGH

1298
00:45:27,600 --> 00:45:30,760
TO KEEP SOMEONE BUSY STUDYING

1299
00:45:30,760 --> 00:45:31,360
THE EFFECTS OF MIRABEGRON ON

1300
00:45:31,360 --> 00:45:32,280
HEALTH.

1301
00:45:32,280 --> 00:45:35,760
WE FREQUENTLY SAMPLED GLUCOSE

1302
00:45:35,760 --> 00:45:37,240
TOLERANCE TEST, THERE WE

1303
00:45:37,240 --> 00:45:38,200
MEASURED THE CAPACITY FOR

1304
00:45:38,200 --> 00:45:40,680
GLUCOSE TO MEDIATE ITS OWN

1305
00:45:40,680 --> 00:45:42,160
DISPOSAL, GLUCOSE INCREASED ITS

1306
00:45:42,160 --> 00:45:44,880
OWN DISPOSAL AFTER THE END OF 28

1307
00:45:44,880 --> 00:45:50,960
DAYS.

1308
00:45:50,960 --> 00:45:53,920
IT ALSO INCREASED INSULIN

1309
00:45:53,920 --> 00:45:56,280
SENSITIVITY IN THE VOLUNTEERS BY

1310
00:45:56,280 --> 00:45:58,800
37%, AND ON THE BETA CELL

1311
00:45:58,800 --> 00:46:01,560
INCREASE, INSULIN PRODUCTION BY

1312
00:46:01,560 --> 00:46:04,200
THE PANCREAS WENT UP BY 37% AND

1313
00:46:04,200 --> 00:46:05,880
DISPOSITION INDEX, BETA CELERY

1314
00:46:05,880 --> 00:46:09,120
SPON SIEVENESS, WENT UP BY 82%.

1315
00:46:09,120 --> 00:46:09,960
SO FOUR WEEKS OF MIRABEGRON

1316
00:46:09,960 --> 00:46:11,600
TREATMENT HAD A LOT OF IMPACT ON

1317
00:46:11,600 --> 00:46:12,200
THE BODY.

1318
00:46:12,200 --> 00:46:15,760
SOME FROM BROWN FAT, SOME FROM

1319
00:46:15,760 --> 00:46:16,480
WHITE FAT, SOME TO BE

1320
00:46:16,480 --> 00:46:16,800
DETERMINED.

1321
00:46:16,800 --> 00:46:20,880
JUST TO COMPARE ON MIRABEGRON

1322
00:46:20,880 --> 00:46:21,840
FOUR WEEKS IS IN RELATION TO

1323
00:46:21,840 --> 00:46:25,280
OTHER TYPES OF HORMONES, THIS IS

1324
00:46:25,280 --> 00:46:28,840
GLP-1 GIVEN INTRAVENOUSLY,

1325
00:46:28,840 --> 00:46:30,240
METFORMIN, BARIATRIC SURGERY,

1326
00:46:30,240 --> 00:46:31,160
AND MILD EXERCISE.

1327
00:46:31,160 --> 00:46:32,880
THESE ARE THE PARAMETERS I

1328
00:46:32,880 --> 00:46:36,120
SHOWED YOU, SG AND SI RELATE TO

1329
00:46:36,120 --> 00:46:37,840
INSULIN SENSITIVITY AND

1330
00:46:37,840 --> 00:46:38,560
MIRABEGRON IS COMPARABLE.

1331
00:46:38,560 --> 00:46:40,960
ON THE BETA CELL SIDE IN TERMS

1332
00:46:40,960 --> 00:46:43,280
OF INSULIN SECRETION, MIRABEGRON

1333
00:46:43,280 --> 00:46:44,760
IS ONCE AGAIN COMPARABLE TO MANY

1334
00:46:44,760 --> 00:46:47,440
OF THESE INTERVENTIONS.

1335
00:46:47,440 --> 00:46:48,560
THIS MAKES MIRABEGRON A

1336
00:46:48,560 --> 00:46:50,080
PROMISING PATHWAY TOWARDS

1337
00:46:50,080 --> 00:46:51,680
TREATING METABOLIC HEALTH AS

1338
00:46:51,680 --> 00:46:53,080
SOON AS WE CAN GET TO A SAFE

1339
00:46:53,080 --> 00:46:54,920
LEVEL.

1340
00:46:54,920 --> 00:46:56,600
SO IN SUMMARY, THE CHRONIC

1341
00:46:56,600 --> 00:46:59,080
MIRABEGRON TREATMENT STUDIES,

1342
00:46:59,080 --> 00:46:59,880
TREATMENTS FOR FOUR WEEKS LED TO

1343
00:46:59,880 --> 00:47:01,880
THE FOLLOWING, AN INCREASE IN

1344
00:47:01,880 --> 00:47:04,080
BROWN FAT METABOLIC ACTIVITY,

1345
00:47:04,080 --> 00:47:05,120
INCREASE IN RESTING ENERGY

1346
00:47:05,120 --> 00:47:06,880
EXPENDITURE I DIDN'T SHOW YOU 6%

1347
00:47:06,880 --> 00:47:08,720
ABOVE BASELINE, INCREASES IN THE

1348
00:47:08,720 --> 00:47:14,040
HDL, THE GOOD CHOLESTEROL, APOE

1349
00:47:14,040 --> 00:47:17,120
AND REDUCTION OF A RATIO THAT IS

1350
00:47:17,120 --> 00:47:18,400
ASSOCIATED WITH CARDIOMETABOLIC

1351
00:47:18,400 --> 00:47:21,080
RISK SO IT'S A GOOD THING THE

1352
00:47:21,080 --> 00:47:22,800
RATIO WENT DOWN.

1353
00:47:22,800 --> 00:47:25,480
THERE WERE IMPROVEMENTS IN

1354
00:47:25,480 --> 00:47:27,200
GLUCOSE UP TAKE AND BETA CELL

1355
00:47:27,200 --> 00:47:27,560
FUNCTION.

1356
00:47:27,560 --> 00:47:29,280
IT WAS NOT YET KNOWN ALL THE

1357
00:47:29,280 --> 00:47:31,040
UNDERLYING MECHANISMS BUT AS WE

1358
00:47:31,040 --> 00:47:32,560
MENTIONED, WE THINK BROWN FAT

1359
00:47:32,560 --> 00:47:33,720
AND WHITE FAT LIKELY HAVE

1360
00:47:33,720 --> 00:47:35,720
IMPORTANT ROLES AND THEREFORE WE

1361
00:47:35,720 --> 00:47:38,600
BELIEVE BETA THREE ADRENERGIC

1362
00:47:38,600 --> 00:47:39,320
REACCEPT INVENTORIES MAY BE A

1363
00:47:39,320 --> 00:47:41,120
NEW APPROACH TO TREATING OBESITY

1364
00:47:41,120 --> 00:47:43,080
RELATED COMPLICATIONS SUCH AS

1365
00:47:43,080 --> 00:47:44,000
TYPE TWO DIABETES AS WELL AS

1366
00:47:44,000 --> 00:47:45,960
COMPONENTS OF THE METABOLIC

1367
00:47:45,960 --> 00:47:47,760
SYNDROME INCLUDING POSSIBLE

1368
00:47:47,760 --> 00:47:50,520
INFERTILITY AS I'LL DESCRIBE AT

1369
00:47:50,520 --> 00:47:51,120
SOME POINT IN THE FUTURE.

1370
00:47:51,120 --> 00:47:52,520
SO NEXT STEPS AND FUTURE

1371
00:47:52,520 --> 00:47:53,360
STUDIES, WHERE DO YOU GO FROM

1372
00:47:53,360 --> 00:47:53,720
HERE?

1373
00:47:53,720 --> 00:47:54,760
ONE OF THE THINGS WE NEED TO DO

1374
00:47:54,760 --> 00:47:55,800
IS TRY TO UNDERSTAND THE

1375
00:47:55,800 --> 00:47:57,000
MECHANISM OF THE DISCOVERIES I

1376
00:47:57,000 --> 00:47:57,880
JUST DESCRIBED.

1377
00:47:57,880 --> 00:48:03,240
SO WORK DONE BY CHERYL CERO, A

1378
00:48:03,240 --> 00:48:03,760
POSTDOCTORAL FELLOW WHO

1379
00:48:03,760 --> 00:48:04,800
COMPLETED HER TIME AND MOVED ON

1380
00:48:04,800 --> 00:48:06,840
TO THE NCI, IN COLLABORATION

1381
00:48:06,840 --> 00:48:08,120
WITH ATCC, A BIOLOGICAL RESOURCE

1382
00:48:08,120 --> 00:48:11,080
CENTER, WE HAVE GENERATED TWO

1383
00:48:11,080 --> 00:48:12,720
DIFFERENT CELL TYPES THAT WILL

1384
00:48:12,720 --> 00:48:15,200
BE AVAILABLE IN THE FUTURE, NEAR

1385
00:48:15,200 --> 00:48:16,600
FUTURE, OF WHITE CELLS AND BROWN

1386
00:48:16,600 --> 00:48:19,280
CELLS THAT CAN BE THEN GROWN IN

1387
00:48:19,280 --> 00:48:22,120
CULTURE TO STUDY HUMAN WHITE AND

1388
00:48:22,120 --> 00:48:23,240
BROWN ADIPOCYTE FUNCTION.

1389
00:48:23,240 --> 00:48:24,360
ONE OF THE THINGS WE'VE BEEN

1390
00:48:24,360 --> 00:48:27,080
ABLE TO DO SO FOR IS THROUGH THE

1391
00:48:27,080 --> 00:48:32,680
BIOINER JE TICS I DESCRIBED.

1392
00:48:32,680 --> 00:48:34,920
HUMAN BROWN ADIPOCYTES HAVE A

1393
00:48:34,920 --> 00:48:36,120
MUCH HIGHER BASAL RESPIRATION

1394
00:48:36,120 --> 00:48:37,840
COMPARED TO WHITE, THERE'S

1395
00:48:37,840 --> 00:48:38,560
HIGHER MAXIMAL RESPIRATION IN

1396
00:48:38,560 --> 00:48:40,280
BROWN COMPARED TO WHITE CELLS,

1397
00:48:40,280 --> 00:48:42,120
THERE'S A HIGHER FLEXIBILITY IN

1398
00:48:42,120 --> 00:48:43,040
FUEL UTILIZATION IN THE BROWN

1399
00:48:43,040 --> 00:48:45,760
COMPARED TO THE WHITE, AND THE

1400
00:48:45,760 --> 00:48:46,920
THERMOGENESIS THAT I MENTIONED

1401
00:48:46,920 --> 00:48:51,680
FROM UCP1 IN BROWN ADIPOCYTES IS

1402
00:48:51,680 --> 00:48:55,880
HAPPENING FROM UCP16789 AND ALSO

1403
00:48:55,880 --> 00:48:57,120
NON-UCP1 SOURCES AND WE'RE GOING

1404
00:48:57,120 --> 00:48:58,640
TO FIND OUT WHAT THEY ARE IN THE

1405
00:48:58,640 --> 00:48:59,480
NEXT MONTHS AND YEARS.

1406
00:48:59,480 --> 00:49:02,200
IN ADDITION, CAN YOU DO

1407
00:49:02,200 --> 00:49:02,960
TRANSCRIPTOMICS, WORKING WITH

1408
00:49:02,960 --> 00:49:05,120
THE ATCC GROUP, WE HAVE GENETIC

1409
00:49:05,120 --> 00:49:08,960
SIGNATURES OF WHITE AND BROWN

1410
00:49:08,960 --> 00:49:09,720
ADIPOCYTES BEFORE

1411
00:49:09,720 --> 00:49:10,840
DIFFERENTIATION AND AFTERWARD.

1412
00:49:10,840 --> 00:49:12,960
AND WE'RE GOING TO STUDY THE

1413
00:49:12,960 --> 00:49:14,120
IMPACT OF ALL THESE GENES IN

1414
00:49:14,120 --> 00:49:15,400
ADDITION TO THE GENETIC

1415
00:49:15,400 --> 00:49:15,680
SIGNATURES.

1416
00:49:15,680 --> 00:49:17,280
SO OUR FUTURE RESEARCH LOOKING

1417
00:49:17,280 --> 00:49:20,200
AT OUR PLATFORM OF INTERRELATED

1418
00:49:20,200 --> 00:49:21,480
PILLARS, WE'RE GOING TO DEVELOP

1419
00:49:21,480 --> 00:49:23,240
MRI IMAGING, WE'RE GOING TO

1420
00:49:23,240 --> 00:49:25,000
LEVERAGE THE CELL LINES TO STUDY

1421
00:49:25,000 --> 00:49:28,200
HUMAN WHITE AND BROWN ADIPOCYTES

1422
00:49:28,200 --> 00:49:28,960
SIGNALING AND SYNTHESIS AND

1423
00:49:28,960 --> 00:49:30,440
WE'RE GOING TO ASSESS

1424
00:49:30,440 --> 00:49:31,720
MIRABEGRON'S ABILITY TO AK VAIT

1425
00:49:31,720 --> 00:49:33,120
WHITE FAT AND BROWN FAT IN

1426
00:49:33,120 --> 00:49:34,760
PATIENTS AND POPULATIONS AT RISK

1427
00:49:34,760 --> 00:49:37,520
FOR METABOLIC DISEASE.

1428
00:49:37,520 --> 00:49:38,800
SO THE FINAL SUMMARY IS THAT

1429
00:49:38,800 --> 00:49:41,680
ADIPOSE TISSUE IS POLYCHROMATIC.

1430
00:49:41,680 --> 00:49:43,880
IT CAN BE WHITE, BEIGE, BROWN

1431
00:49:43,880 --> 00:49:46,880
AND EVEN MORE.

1432
00:49:46,880 --> 00:49:48,680
EACH TISSUE CONTAINS MULTIPLE

1433
00:49:48,680 --> 00:49:49,280
CELL TYPES.

1434
00:49:49,280 --> 00:49:51,600
WHITE ADIPOSE TISSUE STORES FAT

1435
00:49:51,600 --> 00:49:53,040
AS A RESERVOIR FOR BOT DE'S

1436
00:49:53,040 --> 00:49:53,960
TISSUE NEEDS.

1437
00:49:53,960 --> 00:49:55,920
BROWN ADIPOSE TISSUE STORES FAT

1438
00:49:55,920 --> 00:49:57,560
TEMPORARILY AS A FUEL TO SUPPORT

1439
00:49:57,560 --> 00:49:58,760
THE GENERATION OF HEAT.

1440
00:49:58,760 --> 00:50:00,480
THE ENDOCRINE ROLES, MANY STILL

1441
00:50:00,480 --> 00:50:02,800
TO BE DETERMINED, RELATE TO

1442
00:50:02,800 --> 00:50:04,160
THEIR OVERALL GOALS, AND

1443
00:50:04,160 --> 00:50:07,360
SOMETHING I LIKE TO CALL A

1444
00:50:07,360 --> 00:50:08,000
TELEOLOGICAL ENDOCRINOLOGY.

1445
00:50:08,000 --> 00:50:10,280
WHAT IS THE IMOAL O GOAL OF THE

1446
00:50:10,280 --> 00:50:11,600
TISSUE AND WHAT KIND OF MESSAGES

1447
00:50:11,600 --> 00:50:13,040
IS IT SENDING?

1448
00:50:13,040 --> 00:50:14,400
BASED ON THE MESSAGES, WE CAN

1449
00:50:14,400 --> 00:50:15,240
LEARN MORE ABOUT WHAT IT'S

1450
00:50:15,240 --> 00:50:16,960
SUPPOSED TO BE DOING.

1451
00:50:16,960 --> 00:50:18,320
OBESITY IS A DISEASE DRIVEN BY

1452
00:50:18,320 --> 00:50:19,800
THE BRAIN THAT IS MANIFESTED AS

1453
00:50:19,800 --> 00:50:22,080
AN EXCESS OF WHITE ADIPOSE

1454
00:50:22,080 --> 00:50:23,480
TISSUE AND A DYSFUNCTION OF THE

1455
00:50:23,480 --> 00:50:25,040
BROWN ADIPOSE TISSUE.

1456
00:50:25,040 --> 00:50:26,600
AND FINALLY, CHRONIC TREATMENT

1457
00:50:26,600 --> 00:50:30,280
WITH BETA THREE ADRENERGIC

1458
00:50:30,280 --> 00:50:33,240
RECEPTOR AGONISTS, AK VAIT BAT

1459
00:50:33,240 --> 00:50:36,720
AND WAA LEADS TO CHANGES IN

1460
00:50:36,720 --> 00:50:38,200
GLUCOMETABOLISM IN THE BODY,

1461
00:50:38,200 --> 00:50:39,320
CHOLESTEROL PROFILE AND OTHER

1462
00:50:39,320 --> 00:50:40,320
RESPONSES WAITING TO BE

1463
00:50:40,320 --> 00:50:41,000
DISCOVERED.

1464
00:50:41,000 --> 00:50:41,840
STAY TUNED FOR MORE!

1465
00:50:41,840 --> 00:50:45,600
SO WITH NA, I WAN THAT, I WANT Y

1466
00:50:45,600 --> 00:50:48,640
GROUP WHO WORKS WITH ME ON A

1467
00:50:48,640 --> 00:50:49,920
REGULAR BASIS, FORMER MEMBERS OF

1468
00:50:49,920 --> 00:50:54,640
THE GROUP HERE, COLLABORATIVE

1469
00:50:54,640 --> 00:51:01,120
WITH THE NIH, HARVARD,

1470
00:51:01,120 --> 00:51:02,320
CEDARS-SINAI AND MCGILL.

1471
00:51:02,320 --> 00:51:05,120
>>THANK YOU VERY MUCH FOR
AN

1472
00:51:05,120 --> 00:51:07,480
EXTRAORDINARILY EXCITING

1473
00:51:07,480 --> 00:51:09,320
BRILLIANT PRESENTATION.

1474
00:51:09,320 --> 00:51:11,760
YOU'VE GIVEN EVERYBODY A LOT TO

1475
00:51:11,760 --> 00:51:13,200
THINK ABOUT, AND WE WILL HAVE

1476
00:51:13,200 --> 00:51:18,200
PLENTY OF QUESTIONS, I'M SURE.

1477
00:51:18,200 --> 00:51:19,920
SO NOW WE'RE GOING TO PROCEED TO

1478
00:51:19,920 --> 00:51:21,080
KEVIN HALL, WHO'S GOING TO

1479
00:51:21,080 --> 00:51:24,640
EXPLAIN TO US HOW DO YOU GET

1480
00:51:24,640 --> 00:51:27,400
THIN AND STAY THAT WAY?

1481
00:51:27,400 --> 00:51:29,800
OR CAN YOU?

1482
00:51:29,800 --> 00:51:31,680
A PHYSICIST'S VIEW.

1483
00:51:31,680 --> 00:51:31,880
KEVIN?

1484
00:51:31,880 --> 00:51:33,760
>>THANKS VERY MUCH, WIN,
AND

1485
00:51:33,760 --> 00:51:36,280
THANKS, AARON, FOR AN EXCELLENT

1486
00:51:36,280 --> 00:51:37,120
INTRODUCTORY TALK HERE.

1487
00:51:37,120 --> 00:51:39,280
IT'S GREAT TO SEE SUCH EXCITING

1488
00:51:39,280 --> 00:51:40,960
RESEARCH FROM MY FRIENDS AND

1489
00:51:40,960 --> 00:51:43,120
COLLABORATORS HERE AT THE NIH.

1490
00:51:43,120 --> 00:51:44,200
SO I DON'T HAVE ANYTHING TO

1491
00:51:44,200 --> 00:51:47,120
DISCLOSE IN TERMS OF FINANCIAL

1492
00:51:47,120 --> 00:51:47,800
DISCLOSURES.

1493
00:51:47,800 --> 00:51:50,480
I WAS PROVIDED THREE LEARNING

1494
00:51:50,480 --> 00:51:52,040
OBJECTIVES WHICH YOU CAN READ IN

1495
00:51:52,040 --> 00:51:53,240
YOUR OWN TIME.

1496
00:51:53,240 --> 00:51:56,240
I WANT TO START OFF BY KIND OF

1497
00:51:56,240 --> 00:51:59,000
FLASHING BACK TO HOW MANY

1498
00:51:59,000 --> 00:52:01,000
PHYSICIANS HAVE THOUGHT ABOUT

1499
00:52:01,000 --> 00:52:01,960
WEIGHT CONTROL AND TREATING

1500
00:52:01,960 --> 00:52:05,600
PEOPLE WITH OBESITY OVER THE

1501
00:52:05,600 --> 00:52:05,920
YEARS.

1502
00:52:05,920 --> 00:52:07,320
THIS HAS REALLY SORT OF

1503
00:52:07,320 --> 00:52:09,000
CULMINATED IN A PIECE PUBLISHED

1504
00:52:09,000 --> 00:52:10,520
IN THE JOURNAL OF THE AMERICAN

1505
00:52:10,520 --> 00:52:11,960
MEDICAL ASSOCIATION BACK IN

1506
00:52:11,960 --> 00:52:13,840
2018, ENTITLED COUNTING CALORIES

1507
00:52:13,840 --> 00:52:15,720
AS AN APPROACH TO ACHIEVE WEIGHT

1508
00:52:15,720 --> 00:52:16,200
CONTROL.

1509
00:52:16,200 --> 00:52:17,880
AND THE IDEA WAS THAT IF A

1510
00:52:17,880 --> 00:52:19,600
PATIENT REDUCES THEIR CALORIC

1511
00:52:19,600 --> 00:52:21,160
INGESTION BY 500-CALORIES PER

1512
00:52:21,160 --> 00:52:23,320
DAY FOR SEVEN DAYS, SHE OR HE

1513
00:52:23,320 --> 00:52:25,760
WOULD LOSE ABOUT 1-POUND OF BODY

1514
00:52:25,760 --> 00:52:26,960
WEIGHT PER WEEK.

1515
00:52:26,960 --> 00:52:30,640
THIS IS AN OLD RULE OF THUMB

1516
00:52:30,640 --> 00:52:32,280
THAT GOES BACK MANY, MANY

1517
00:52:32,280 --> 00:52:33,040
DECADES.

1518
00:52:33,040 --> 00:52:34,160
DIETITIANS ARE TESTED ON THIS

1519
00:52:34,160 --> 00:52:35,080
RULE, PEOPLE HAVE BEEN USING

1520
00:52:35,080 --> 00:52:37,320
THIS RULE OF THUMB TO PREDICT

1521
00:52:37,320 --> 00:52:38,720
HOW PEOPLE MIGHT CHANGE THEIR

1522
00:52:38,720 --> 00:52:40,080
WEIGHT OVER TIME BY MAKING

1523
00:52:40,080 --> 00:52:44,920
CHANGES IN THEIR DIET, POLG SEE

1524
00:52:44,920 --> 00:52:45,880
MAKERS HAVE USED THIS RULE OF

1525
00:52:45,880 --> 00:52:47,440
THUMB TO PREDICT WHAT WOULD

1526
00:52:47,440 --> 00:52:54,280
HAPPEN WITH A SODA TAX IN THE

1527
00:52:54,280 --> 00:52:55,440
OBESITY COMMUNITY.

1528
00:52:55,440 --> 00:52:56,400
THE PROBLEM WITH THIS RULE OF

1529
00:52:56,400 --> 00:52:57,960
THUMB IS IT'S JUST PLAIN WRONG.

1530
00:52:57,960 --> 00:52:59,120
AND IT DOESN'T TAKE A LOT OF

1531
00:52:59,120 --> 00:53:01,200
THINKING TO REALIZE THAT

1532
00:53:01,200 --> 00:53:01,800
SOMETHING MUST BE WRONG WITH

1533
00:53:01,800 --> 00:53:03,120
THIS RULE OF THUMB.

1534
00:53:03,120 --> 00:53:05,040
BECAUSE IF YOU IMAGINE THAT YOU

1535
00:53:05,040 --> 00:53:08,160
ARE A MAN, SAY, THAT WEIGHS

1536
00:53:08,160 --> 00:53:10,320
100-KILOGRAMS AND IS EATING

1537
00:53:10,320 --> 00:53:13,120
ABOUT 3,000KILLICALORIES PER DAY

1538
00:53:13,120 --> 00:53:14,480
AND YOU PUT THAT MAN ON A DIET

1539
00:53:14,480 --> 00:53:19,840
BY CUTTING THEIR CALORIES BY 500

1540
00:53:19,840 --> 00:53:21,240
KILLICALORIES PER DAY SUCH THAT

1541
00:53:21,240 --> 00:53:26,000
NOW THEY'RE EATING 25, THIS

1542
00:53:26,000 --> 00:53:29,800
PREDICTS THAT PERSON WOULD

1543
00:53:29,800 --> 00:53:30,480
DISAPPEAR AFTER FOUR YEARS SO

1544
00:53:30,480 --> 00:53:31,880
SOMETHING IS CLEARLY WRONG WITH

1545
00:53:31,880 --> 00:53:34,000
THIS MODEL OF HOW THE

1546
00:53:34,000 --> 00:53:35,880
RELATIONSHIP BETWEEN CALORIE

1547
00:53:35,880 --> 00:53:38,560
INTAKE AND BODY WEIGHT IS

1548
00:53:38,560 --> 00:53:39,280
RELATED.

1549
00:53:39,280 --> 00:53:41,080
AND ONE OF THE REASONS IT'S

1550
00:53:41,080 --> 00:53:41,880
WRONG, THE MAIN REASON IT'S

1551
00:53:41,880 --> 00:53:43,640
WRONG IS IT TREATS CALORIE

1552
00:53:43,640 --> 00:53:46,280
INTAKE AND CALORIE EXPENDITURE

1553
00:53:46,280 --> 00:53:47,800
AS INDEPENDENT QUANTITIES.

1554
00:53:47,800 --> 00:53:49,000
WHEREAS IF YOU CHANGE ONE,

1555
00:53:49,000 --> 00:53:50,600
NOTHING HAPPENS TO THE OTHER,

1556
00:53:50,600 --> 00:53:52,760
AND BECAUSE WE HAVE A LAW OF

1557
00:53:52,760 --> 00:53:54,880
CONSERVATION OF ENERGY, I'M A

1558
00:53:54,880 --> 00:53:56,240
PHYSICIST BY TRAINING SO THAT'S

1559
00:53:56,240 --> 00:53:59,000
ALSO CALLED THE FIRST LAW OF

1560
00:53:59,000 --> 00:54:00,240
THERMODYNAMICS, THE IDEA IS IF

1561
00:54:00,240 --> 00:54:02,360
YOU OFFSET THE CALORIE INTAKE

1562
00:54:02,360 --> 00:54:03,240
FROM CALORIE EXPENDITURE BY

1563
00:54:03,240 --> 00:54:05,120
CUTTING THE CALORIES IN THE

1564
00:54:05,120 --> 00:54:06,880
DIET, THEN THIS RULE OF THUMB

1565
00:54:06,880 --> 00:54:09,840
PREDIBTS THAT NPRETICKETS THAT S

1566
00:54:09,840 --> 00:54:11,080
TO THE CALORIE EXPENDITURE OF

1567
00:54:11,080 --> 00:54:12,080
THE BODY SO THEREFORE THE BODY

1568
00:54:12,080 --> 00:54:13,600
HAS TO MAKE UP THE DEFICIT OF

1569
00:54:13,600 --> 00:54:16,600
CALORIES COMING IN THE DIET BY

1570
00:54:16,600 --> 00:54:18,000
MOBILIZING PRIMARILY BODY FAT TO

1571
00:54:18,000 --> 00:54:19,240
MAKE UP THAT DIFFERENCE AND THAT

1572
00:54:19,240 --> 00:54:20,720
GIVES RISE TO THIS LINEAR RATE

1573
00:54:20,720 --> 00:54:22,000
OF WEIGHT LOSS.

1574
00:54:22,000 --> 00:54:23,720
THE PROBLEM, OF COURSE, IS THAT

1575
00:54:23,720 --> 00:54:25,120
CALORIE INTAKE AND CALORIE

1576
00:54:25,120 --> 00:54:28,200
EXPENDITURE ARE NOT INDEPENDENT,

1577
00:54:28,200 --> 00:54:29,440
THAT THEY ARE ACTUALLY

1578
00:54:29,440 --> 00:54:30,520
INTERRELATED IN A VERY

1579
00:54:30,520 --> 00:54:32,800
INTERESTING WAY.

1580
00:54:32,800 --> 00:54:33,920
AND A VERY COMPLEX WAY THAT WE

1581
00:54:33,920 --> 00:54:35,320
DON'T FULLY UNDERSTAND, TO BE

1582
00:54:35,320 --> 00:54:35,640
HONEST.

1583
00:54:35,640 --> 00:54:36,760
ONE OF THE THINGS WE DO

1584
00:54:36,760 --> 00:54:38,400
UNDERSTAND IS THAT TISSUES LIKE

1585
00:54:38,400 --> 00:54:39,600
ADIPOSE TISSUE THAT WE JUST

1586
00:54:39,600 --> 00:54:42,240
HEARD A WONDERFUL LECTURE ABOUT,

1587
00:54:42,240 --> 00:54:44,840
SECRETE ADIP KINES, ONE OF WHICH

1588
00:54:44,840 --> 00:54:47,040
IS LEPTINS DISCOVERED A COUPLE

1589
00:54:47,040 --> 00:54:51,320
DECADES AGO OR SO, AND THOSE

1590
00:54:51,320 --> 00:54:52,680
HORMONES FROM ADIPOCYTES AS WELL

1591
00:54:52,680 --> 00:54:54,920
AS OTHER AREAS OF THE BODY LIKE

1592
00:54:54,920 --> 00:54:56,960
THE GUT, IMPINGE ON REGIONS OF

1593
00:54:56,960 --> 00:55:00,320
THE BRAIN TO MODULATE CALORIE

1594
00:55:00,320 --> 00:55:01,560
EXPENDITURE AND ALSO APPETITE

1595
00:55:01,560 --> 00:55:03,160
CALORIE INTAKE IN SUCH A WAY

1596
00:55:03,160 --> 00:55:05,040
THAT YOU HAVE ESSENTIALLY A PAIR

1597
00:55:05,040 --> 00:55:07,600
OF NEGATIVE FEEDBACK CONTROL

1598
00:55:07,600 --> 00:55:08,840
LOOPS THAT ARE GOVERNING BOTH

1599
00:55:08,840 --> 00:55:11,000
THE CALORIE INTAKE SIDE OF THE

1600
00:55:11,000 --> 00:55:12,240
EQUATION AND THE CALORIE

1601
00:55:12,240 --> 00:55:15,640
EXPENDITURE SIDE OF THE EQUATION

1602
00:55:15,640 --> 00:55:17,080
TO OFFSET ANY CHANGES THAT ONE

1603
00:55:17,080 --> 00:55:19,160
MIGHT TRY TO MAKE IN EITHER THE

1604
00:55:19,160 --> 00:55:20,920
EXPENDITURE SIDE OR THE INTAKE

1605
00:55:20,920 --> 00:55:23,080
SIDE, THE BODY FIGHTS BACK IN

1606
00:55:23,080 --> 00:55:24,400
SOME WAY AGAINST THOSE

1607
00:55:24,400 --> 00:55:25,280
PERTURBATIONS.

1608
00:55:25,280 --> 00:55:29,000
SO ONE OF THE THINGS THAT I'VE

1609
00:55:29,000 --> 00:55:30,520
BEEN DOING IN MY LAB AT THE NIH

1610
00:55:30,520 --> 00:55:32,120
FOR MANY, MANY YEARS HAS BEEN

1611
00:55:32,120 --> 00:55:33,520
TRYING TO BUILD MATHEMATICAL

1612
00:55:33,520 --> 00:55:34,960
MODELS OF THE PHYSIOLOGY OF

1613
00:55:34,960 --> 00:55:37,040
THESE FEEDBACK LOOPS AND TO TRY

1614
00:55:37,040 --> 00:55:39,200
TO QUANTIFY THEIR STRENGTH.

1615
00:55:39,200 --> 00:55:41,200
AS WELL AS ANALYZE DATA

1616
00:55:41,200 --> 00:55:42,480
COLLECTED IN PEOPLE WHO ARE

1617
00:55:42,480 --> 00:55:44,400
TRYING TO CHANGE THEIR WEIGHT

1618
00:55:44,400 --> 00:55:46,200
AND QUANTIFY HOW THESE DIFFERENT

1619
00:55:46,200 --> 00:55:47,920
FEEDBACK LOOPS RESPOND TO THEIR

1620
00:55:47,920 --> 00:55:50,240
EFFORTS TO CHANGE WEIGHT.

1621
00:55:50,240 --> 00:55:52,960
SO ONE OF THE MORE POPULAR

1622
00:55:52,960 --> 00:55:55,520
EXAMPLES OF THAT, THAT WE'VE

1623
00:55:55,520 --> 00:55:57,200
STUDIED, WAS CONTESTANTS ON A

1624
00:55:57,200 --> 00:55:58,040
TELEVISION PROGRAM CALLED THE

1625
00:55:58,040 --> 00:56:01,520
BIGGEST LOSER, WHICH WAS A

1626
00:56:01,520 --> 00:56:03,560
NATIONAL TELEVISED WEIGHT LOSS

1627
00:56:03,560 --> 00:56:04,520
COMPETITION FOR MANY, MANY

1628
00:56:04,520 --> 00:56:07,600
YEARS, AND WE STUDIED SEASON

1629
00:56:07,600 --> 00:56:08,960
8 CONTESTANTS OF THE BIGGEST

1630
00:56:08,960 --> 00:56:09,200
LOSER.

1631
00:56:09,200 --> 00:56:11,840
AND HERE'S THE WINNER OF THAT

1632
00:56:11,840 --> 00:56:12,840
SEASON OF THE BIGGEST LOSER.

1633
00:56:12,840 --> 00:56:16,320
THIS IS DANNY CAHILL.

1634
00:56:16,320 --> 00:56:18,400
HE LOST 239 POUNDS OVER THE

1635
00:56:18,400 --> 00:56:22,040
COURSE OF SEVEN SMON MONTHS ON S

1636
00:56:22,040 --> 00:56:23,320
CRAZY FAT SHAMING TELEVISION

1637
00:56:23,320 --> 00:56:24,760
PROGRAM, WHICH I DON'T ENDORSE

1638
00:56:24,760 --> 00:56:26,400
THE METHODS THAT WERE USED BUT I

1639
00:56:26,400 --> 00:56:28,680
THOUGHT IT WAS A REALLY

1640
00:56:28,680 --> 00:56:30,800
WONDERFUL WAY TO KIND OF STUDY

1641
00:56:30,800 --> 00:56:34,320
THESE FEEDBACK CIRCUITS THAT I

1642
00:56:34,320 --> 00:56:36,960
WAS TALKING ABOUT A MOMENT AGO.

1643
00:56:36,960 --> 00:56:38,880
AND TRY TO QUANTIFY THEM IN AN

1644
00:56:38,880 --> 00:56:41,400
ACTUAL STUDY WHERE WE SENT

1645
00:56:41,400 --> 00:56:43,040
POSTDOCS OUT TO THIS RANCH IN

1646
00:56:43,040 --> 00:56:44,400
MALIBU, WHERE THIS PROGRAM WAS

1647
00:56:44,400 --> 00:56:46,600
BEING FILMED, WE MEASURED USING

1648
00:56:46,600 --> 00:56:48,600
A VARIETY OF THE METHODS THAT

1649
00:56:48,600 --> 00:56:50,760
AARON NICE LEGAL SUMMARIZED,

1650
00:56:50,760 --> 00:56:52,200
ENERGY EXPENDITURE, BODY

1651
00:56:52,200 --> 00:56:54,320
COMPOSITION CHANGES, BOTH IN

1652
00:56:54,320 --> 00:56:55,840
THESE FOLKS AS THEY UNDERWENT

1653
00:56:55,840 --> 00:56:57,920
THIS CRAZY WEIGHT LOSS

1654
00:56:57,920 --> 00:56:58,920
COMPETITION, AND THEN MANY YEARS

1655
00:56:58,920 --> 00:56:59,440
LATER.

1656
00:56:59,440 --> 00:57:00,560
AND I'LL SHARE WITH YOU SOME OF

1657
00:57:00,560 --> 00:57:02,760
THE DATA THAT WE MEASURED AND

1658
00:57:02,760 --> 00:57:05,040
SOME OF OUR MATH MACKALL MODEL

1659
00:57:05,040 --> 00:57:07,400
SIMULATIONS OF WHAT WE THINK

1660
00:57:07,400 --> 00:57:08,840
HAPPENED IN TERMS OF THEIR

1661
00:57:08,840 --> 00:57:09,440
PHYSIOLOGY.

1662
00:57:09,440 --> 00:57:11,000
BUT THESE ARE THE MEAN DATA IN

1663
00:57:11,000 --> 00:57:13,560
THE BOXES FOR BODY WEIGHT AND

1664
00:57:13,560 --> 00:57:15,840
FAT MASS ALONG WITH OUR

1665
00:57:15,840 --> 00:57:16,840
COMPUTATIONAL MODEL SIMULATIONS

1666
00:57:16,840 --> 00:57:19,080
OF WHAT HAPPENED IN THESE FOLKS.

1667
00:57:19,080 --> 00:57:21,160
SO FOR THE FIRST 13 WEEKS,

1668
00:57:21,160 --> 00:57:22,160
THEY'RE ISOLATED ON THIS RANCH

1669
00:57:22,160 --> 00:57:24,000
IN MALIBU, AND THEY'RE

1670
00:57:24,000 --> 00:57:25,200
UNDERGOING BASICALLY A WEIGHT

1671
00:57:25,200 --> 00:57:27,040
LOSS COMPETITION AND THEY'RE

1672
00:57:27,040 --> 00:57:29,320
LOSING WEIGHT AT AN ASTONISHING

1673
00:57:29,320 --> 00:57:30,680
RATE OF ABOUT A POUND A DAY OVER

1674
00:57:30,680 --> 00:57:32,560
THE COURSE OF THIS 13-WEEK

1675
00:57:32,560 --> 00:57:32,800
PERIOD.

1676
00:57:32,800 --> 00:57:34,120
AND YOU CAN SEE IT'S A PRETTY

1677
00:57:34,120 --> 00:57:35,800
LINEAR RATE OF WEIGHT LOSS OVER

1678
00:57:35,800 --> 00:57:37,600
13 WEEKS AND THAT THE VAST

1679
00:57:37,600 --> 00:57:38,840
MAJORITY OF THE WEIGHT LOSS IS

1680
00:57:38,840 --> 00:57:41,400
COMING FROM LOSS OF BODY FAT.

1681
00:57:41,400 --> 00:57:43,760
WHICH IS THE GREEN CURVE IN OPEN

1682
00:57:43,760 --> 00:57:45,680
BOXES HERE.

1683
00:57:45,680 --> 00:57:47,520
THESE FOLKS ARE BASICALLY THEN

1684
00:57:47,520 --> 00:57:50,600
SENT HOME FOR ANOTHER PERIOD OF

1685
00:57:50,600 --> 00:57:52,520
TIME BEFORE THEY'RE CALLED BACK

1686
00:57:52,520 --> 00:57:54,200
TO THE FINALE THE PROGRAM AND

1687
00:57:54,200 --> 00:57:54,880
THEY'RE STILL IN THIS

1688
00:57:54,880 --> 00:57:55,840
COMPETITION AND THEY'RE TOLD

1689
00:57:55,840 --> 00:57:58,360
JUST KEEP IT UP AT HOME, KEEP

1690
00:57:58,360 --> 00:58:00,200
DOING YOUR EXERCISE, KEEP DOING

1691
00:58:00,200 --> 00:58:01,400
YOUR DIET, AND YOU CAN SEE THAT

1692
00:58:01,400 --> 00:58:04,240
THE RATE OF WEIGHT LOSS AND FAT

1693
00:58:04,240 --> 00:58:05,680
MASS LOSS SLOWS DOWN SLIGHTLY SO

1694
00:58:05,680 --> 00:58:08,600
IT'S ONLY ABOUT HALF A POUND A

1695
00:58:08,600 --> 00:58:10,080
DAY EVERY DAY, WHICH IS PRETTY

1696
00:58:10,080 --> 00:58:11,440
CRAZY, WHEN YOU THINK ABOUT THE

1697
00:58:11,440 --> 00:58:13,920
SHEER MAGNITUDE OF THAT.

1698
00:58:13,920 --> 00:58:15,680
AND THEN THEY CAME BACK AT THE

1699
00:58:15,680 --> 00:58:21,360
FINALE AFTER 30 WEEKS OR ABOUT .

1700
00:58:21,360 --> 00:58:23,120
NOW, UNDERLYING THESE WEIGHT AND

1701
00:58:23,120 --> 00:58:26,640
FAT MASS TRAJECTORIES, WHAT WE

1702
00:58:26,640 --> 00:58:27,600
MEASURED WAS HOW MANY TOTAL

1703
00:58:27,600 --> 00:58:28,880
CALORIES PER DAY THAT THEY WERE

1704
00:58:28,880 --> 00:58:29,360
EXPENDING.

1705
00:58:29,360 --> 00:58:31,400
AND WE USE THE DOUBLY LABELED

1706
00:58:31,400 --> 00:58:32,320
WATER METHOD THAT AARON

1707
00:58:32,320 --> 00:58:33,160
MENTIONED VERY BRIEFLY AND I'M

1708
00:58:33,160 --> 00:58:34,440
NOT GOING TO GO INTO DETAILS

1709
00:58:34,440 --> 00:58:35,680
ABOUT HOW IT WORKS, BUT BEFORE

1710
00:58:35,680 --> 00:58:37,120
THE COMPETITION, BEFORE THEY

1711
00:58:37,120 --> 00:58:40,280
WERE ENGAGING IN THIS PROGRAM,

1712
00:58:40,280 --> 00:58:44,080
THESE FOLKS HAD A BODY MASS OF

1713
00:58:44,080 --> 00:58:46,120
ABOUT 140 KILOS.

1714
00:58:46,120 --> 00:58:47,880
THEY WERE BURNING ABOUT

1715
00:58:47,880 --> 00:58:49,160
3700-CALORIES PER DAY AT THE

1716
00:58:49,160 --> 00:58:49,840
START.

1717
00:58:49,840 --> 00:58:51,000
SIX WEEKS IN TO THIS

1718
00:58:51,000 --> 00:58:51,880
COMPETITION, WHILE THEY'RE STILL

1719
00:58:51,880 --> 00:58:54,960
AT THIS RANCH IN MALIBU, ENERGY

1720
00:58:54,960 --> 00:58:55,960
EXPENDITURE, TOTAL NUMBER OF

1721
00:58:55,960 --> 00:58:58,200
CALORIES THAT THEY WERE BURNING

1722
00:58:58,200 --> 00:58:59,840
GOES UP BY ALMOST A THOUSAND

1723
00:58:59,840 --> 00:59:01,160
CALORIES PER DAY, AND THEN BY

1724
00:59:01,160 --> 00:59:03,160
THE END OF THIS 30-WEEK

1725
00:59:03,160 --> 00:59:04,400
COMPETITION, THE TOTAL NUMBER OF

1726
00:59:04,400 --> 00:59:06,520
CALORIES PER DAY HAS DROPPED TO

1727
00:59:06,520 --> 00:59:08,240
ABOUT 3,000-CALORIES PER DAY.

1728
00:59:08,240 --> 00:59:10,080
AND UNDERLYING THAT, WE CAN USE

1729
00:59:10,080 --> 00:59:11,440
OUR MATHEMATICAL MODEL

1730
00:59:11,440 --> 00:59:14,040
SIMULATIONS TO ESTIMATE WHAT

1731
00:59:14,040 --> 00:59:15,200
CONTRIBUTION WAS DUE TO

1732
00:59:15,200 --> 00:59:15,720
EXERCISE.

1733
00:59:15,720 --> 00:59:16,840
SO THESE FOLKS WEREN'T

1734
00:59:16,840 --> 00:59:19,680
EXERCISING AT ALL BEFORE THE

1735
00:59:19,680 --> 00:59:21,560
COMPETITION, AND THEY QUICKLY

1736
00:59:21,560 --> 00:59:24,160
RAMPED UP THEIR EXERCISE SO THAT

1737
00:59:24,160 --> 00:59:27,000
BY 6 TO 8 WEEKS, THEY'RE JUST IN

1738
00:59:27,000 --> 00:59:29,560
THE EXERCISE BURNING ABOUT 2,000

1739
00:59:29,560 --> 00:59:30,880
KILL CALORIES PER DAY.

1740
00:59:30,880 --> 00:59:33,480
NOW, ANY OF YOU EXERCISERS OUT

1741
00:59:33,480 --> 00:59:35,680
THERE WHO MIGHT HOP ON A

1742
00:59:35,680 --> 00:59:36,880
TREADMILL KNOW THAT THAT'S AN

1743
00:59:36,880 --> 00:59:39,720
ASTONISHING AMOUNT OF EXERCISE.

1744
00:59:39,720 --> 00:59:40,960
IT WORKS OUT TO ABOUT THREE

1745
00:59:40,960 --> 00:59:42,440
HOURS PER DAY EVERY DAY SEVEN

1746
00:59:42,440 --> 00:59:44,800
DAYS A WEEK.

1747
00:59:44,800 --> 00:59:45,360
OF EXERCISE.

1748
00:59:45,360 --> 00:59:48,080
THAT'S NOT ACCOUNTING FOR JUST

1749
00:59:48,080 --> 00:59:51,640
WALKING AROUND FROM PLACE TO

1750
00:59:51,640 --> 00:59:51,880
PLACE.

1751
00:59:51,880 --> 00:59:52,880
THAT'S JUST THE EXERCISE

1752
00:59:52,880 --> 00:59:53,160
COMPONENT.

1753
00:59:53,160 --> 00:59:54,440
YOU CAN SEE AFTER THEY GO HOME,

1754
00:59:54,440 --> 00:59:59,000
THE AMOUNT OF EXERCISE QOAS DOWN

1755
00:59:59,000 --> 01:00:00,080
SLIGHTLY BUT STILL ACCOUNTS FOR

1756
01:00:00,080 --> 01:00:02,360
ABOUT AN HOUR OF VIGOROUS

1757
01:00:02,360 --> 01:00:04,640
EXERCISE EVERY DAY SEVEN DAYS A

1758
01:00:04,640 --> 01:00:05,760
WEEK.

1759
01:00:05,760 --> 01:00:08,240
THE REASON WHY IT GOES DOWN MUCH

1760
01:00:08,240 --> 01:00:09,600
MORCH YOU MIGHT EXPECT BASED ON

1761
01:00:09,600 --> 01:00:12,680
THE ORIGINAL AMOUNT AT 6 TO

1762
01:00:12,680 --> 01:00:16,320
8 WEEKS IS BECAUSE THE ENERGY

1763
01:00:16,320 --> 01:00:18,600
COST OF PHYSICAL ACTIVITY AND

1764
01:00:18,600 --> 01:00:20,040
EXERCISE IS PROPORTIONAL TO THE

1765
01:00:20,040 --> 01:00:20,920
AMOUNT OF BODY WEIGHT THAT

1766
01:00:20,920 --> 01:00:21,320
PEOPLE HAVE.

1767
01:00:21,320 --> 01:00:23,200
SO IT'S A LITTLE BIT UNFAIR, BUT

1768
01:00:23,200 --> 01:00:24,640
FOR THE SAME INTENSITY AND

1769
01:00:24,640 --> 01:00:28,520
DURATION OF EXERCISE, A PESH

1770
01:00:28,520 --> 01:00:29,600
LOSING WEIGHT WILL BURN FEWER

1771
01:00:29,600 --> 01:00:34,160
AND FEWER CALORIES IN EXERCISE.

1772
01:00:34,160 --> 01:00:36,440
I SHOWED YOU IN THE PREVIOUS

1773
01:00:36,440 --> 01:00:37,920
GRAPH THESE FOLKS NE END ON

1774
01:00:37,920 --> 01:00:39,680
AVERAGE HAD LOST 60-KILOS OF

1775
01:00:39,680 --> 01:00:42,240
BODY WEIGHT, SO 122 POUNDS ON

1776
01:00:42,240 --> 01:00:43,600
AVERAGE, AND THAT GIVES RISE TO

1777
01:00:43,600 --> 01:00:46,000
A DECREASE IN THE ENERGY

1778
01:00:46,000 --> 01:00:47,760
EXPENDITURE OF PHYSICAL

1779
01:00:47,760 --> 01:00:48,200
ACTIVITY.

1780
01:00:48,200 --> 01:00:50,360
WE ALSO MEASURED THEIR RESTING

1781
01:00:50,360 --> 01:00:54,440
METABOLIC RATE THROUGH INDIRECT

1782
01:00:54,440 --> 01:00:54,800
CALORIMETRY.

1783
01:00:54,800 --> 01:00:56,160
WHAT WE FOUND IS THEY HAD A

1784
01:00:56,160 --> 01:00:57,840
SUPPRESSION OF RESTING METABOLIC

1785
01:00:57,840 --> 01:00:59,040
RATE THAT I'LL TALK A LITTLE BIT

1786
01:00:59,040 --> 01:01:01,960
MORE ABOUT IN THE NEXT SLIDE.

1787
01:01:01,960 --> 01:01:03,600
BUT THEN WE COULD ALSO CALCULATE

1788
01:01:03,600 --> 01:01:04,720
HOW MANY TOTAL CALORIES THAT

1789
01:01:04,720 --> 01:01:06,000
THEY WERE EATING.

1790
01:01:06,000 --> 01:01:09,120
AGAIN, APPLYING THAT LAW OF

1791
01:01:09,120 --> 01:01:10,520
ENERGY CONSERVATION, AND DURING

1792
01:01:10,520 --> 01:01:11,680
THE PERIOD OF TIME THAT THEY'RE

1793
01:01:11,680 --> 01:01:13,520
ON THE RANCH, WHEN THEY'RE DOING

1794
01:01:13,520 --> 01:01:15,080
THIS INCREDIBLE AMOUNT OF

1795
01:01:15,080 --> 01:01:16,600
EXERCISE, THEY'RE ONLY EATING

1796
01:01:16,600 --> 01:01:19,880
ABOUT 1100-CALORIES PER DAY.

1797
01:01:19,880 --> 01:01:21,120
SO A VERY, VERY SMALL AMOUNT OF

1798
01:01:21,120 --> 01:01:21,480
FOOD.

1799
01:01:21,480 --> 01:01:23,440
AND THEN WHEN THEY GO HOME, THAT

1800
01:01:23,440 --> 01:01:26,000
INCREASES SLIGHTLY, BUT IT'S

1801
01:01:26,000 --> 01:01:27,640
STILL WELL BELOW 2,000-CALORIES

1802
01:01:27,640 --> 01:01:28,040
PER DAY.

1803
01:01:28,040 --> 01:01:29,520
IT'S ABOUT 1900-CALORIES PER

1804
01:01:29,520 --> 01:01:29,720
DAY.

1805
01:01:29,720 --> 01:01:32,480
SO THIS IS A CLEARLY

1806
01:01:32,480 --> 01:01:35,440
UNSUSTAINABLE DIET AND EXERCISE

1807
01:01:35,440 --> 01:01:36,040
INTERVENTION.

1808
01:01:36,040 --> 01:01:37,240
IT JUST KIND OF SHOWS THE FACT

1809
01:01:37,240 --> 01:01:39,680
THAT THESE FOLKS ON -- THESE ARE

1810
01:01:39,680 --> 01:01:42,120
THE AVERAGE DATA, CAN ENGAGE IN

1811
01:01:42,120 --> 01:01:45,160
SUCH INCREDIBLE INTERVENTIONS IN

1812
01:01:45,160 --> 01:01:46,320
BOTH THEIR DIET AND THEIR

1813
01:01:46,320 --> 01:01:47,920
PHYSICAL ACTIVITY SHOWS THAT

1814
01:01:47,920 --> 01:01:49,360
REALLY THESE FOLKS WHO CLEARLY

1815
01:01:49,360 --> 01:01:51,320
HAD OBESITY AT THE BEGINNING OF

1816
01:01:51,320 --> 01:01:53,760
THIS PROGRAM, THEY DID NOT LACK

1817
01:01:53,760 --> 01:01:55,600
WIWILLPOWER.

1818
01:01:55,600 --> 01:01:56,400
THESE ARE FOLKS WHO HAVE

1819
01:01:56,400 --> 01:01:58,360
ENORMOUS AMOUNTS OF WILL POWER.

1820
01:01:58,360 --> 01:01:59,680
BUT WE WERE INTERESTED IN

1821
01:01:59,680 --> 01:02:01,520
INVESTIGATING SOME OF THE

1822
01:02:01,520 --> 01:02:02,840
PHYSIOLOGY UNDERLYING THE

1823
01:02:02,840 --> 01:02:04,040
CHANGES IN RESTING ENERGY

1824
01:02:04,040 --> 01:02:04,360
EXPENDITURE.

1825
01:02:04,360 --> 01:02:06,680
SO WHAT I'M PLOTTING HERE IS THE

1826
01:02:06,680 --> 01:02:08,520
RESTING METABOLIC RATE AT

1827
01:02:08,520 --> 01:02:09,960
BASELINE BEFORE THESE FOLKS

1828
01:02:09,960 --> 01:02:11,720
ENGAGED IN ANY OF THIS CRAZY

1829
01:02:11,720 --> 01:02:13,360
DIET AND EXERCISE PROGRAM, AND

1830
01:02:13,360 --> 01:02:15,080
I'M PLOTTING IT AGAINST THE

1831
01:02:15,080 --> 01:02:16,480
GREATEST DETERMINANT OF RESTING

1832
01:02:16,480 --> 01:02:18,200
ENERGY EXPENDITURE, WHICH IS

1833
01:02:18,200 --> 01:02:19,040
THEIR FAT FREE MASS.

1834
01:02:19,040 --> 01:02:21,000
SO THIS IS THEIR TOTAL BODY

1835
01:02:21,000 --> 01:02:22,080
WEIGHT MINUS THE AMOUNT OF FAT

1836
01:02:22,080 --> 01:02:24,160
THAT THEY HAVE ON THEIR BODY.

1837
01:02:24,160 --> 01:02:25,800
COUNTLESS NUMBER OF STUDIES HAVE

1838
01:02:25,800 --> 01:02:28,240
SHOWN THAT THE BEST PREDICTOR OF

1839
01:02:28,240 --> 01:02:29,680
RESTING METABOLIC RATE IS NOT

1840
01:02:29,680 --> 01:02:31,880
YOUR WEIGHT, IT'S NOT YOUR

1841
01:02:31,880 --> 01:02:33,600
HEIGHT, IT'S NOT YOUR SEX, IT'S

1842
01:02:33,600 --> 01:02:35,480
BASICALLY YOUR FAT FREE MASS.

1843
01:02:35,480 --> 01:02:37,080
AND SO WHAT WE'RE SHOWING HERE

1844
01:02:37,080 --> 01:02:38,920
IS THAT THERE'S A LINEAR

1845
01:02:38,920 --> 01:02:39,760
RELATIONSHIP BETWEEN FAT FREE

1846
01:02:39,760 --> 01:02:41,200
MASS AND RESTING METABOLIC RATE,

1847
01:02:41,200 --> 01:02:42,520
AND THESE ARE ALL THE BASELINE

1848
01:02:42,520 --> 01:02:43,920
DATA FOR THE BIGGEST LOSER

1849
01:02:43,920 --> 01:02:44,400
SUBJECTS.

1850
01:02:44,400 --> 01:02:46,120
THE SLOPE OF THE LINE IS VERY

1851
01:02:46,120 --> 01:02:48,560
CONSISTENT FROM STUDY TO STUDY.

1852
01:02:48,560 --> 01:02:50,200
AND WHAT WE WOULD THEN PREDICT

1853
01:02:50,200 --> 01:02:53,320
IS THAT IF PEOPLE WERE TO LOSE

1854
01:02:53,320 --> 01:02:55,840
WEIGHT, THEY WOULD LOSE BOTH FAT

1855
01:02:55,840 --> 01:02:57,160
MASS AND FAT FREE MASS, AND

1856
01:02:57,160 --> 01:02:58,600
THERE IS A PREDICTION ABOUT WHAT

1857
01:02:58,600 --> 01:03:00,320
SHOULD HAPPEN TO THEIR RESTING

1858
01:03:00,320 --> 01:03:00,960
METABOLIC RATE.

1859
01:03:00,960 --> 01:03:02,200
AND SO FOR EXAMPLE, THIS PERSON

1860
01:03:02,200 --> 01:03:03,960
WHO STARTS AT THE TOP OF THIS

1861
01:03:03,960 --> 01:03:06,600
LINE THAT'S VERY CLOSE TO THE

1862
01:03:06,600 --> 01:03:07,720
LINE, IF THEY LOSE A CERTAIN

1863
01:03:07,720 --> 01:03:08,680
AMOUNT OF FAT FREE MASS THEY

1864
01:03:08,680 --> 01:03:09,880
WOULD BE PREDICTED TO JUST SLIDE

1865
01:03:09,880 --> 01:03:11,080
ALONG THE LINE AND LOSE A

1866
01:03:11,080 --> 01:03:12,920
CERTAIN AMOUNT OF THEIR RESTING

1867
01:03:12,920 --> 01:03:14,600
ENERGY EXPENDITURE CORRESPONDING

1868
01:03:14,600 --> 01:03:16,960
TO THE LOSS OF FAT FREE MASS.

1869
01:03:16,960 --> 01:03:17,880
SO ONE OF THE THINGS WE WANTED

1870
01:03:17,880 --> 01:03:20,040
TO TEST WAS, DID THESE FOLKS WHO

1871
01:03:20,040 --> 01:03:23,680
ENGAGED IN THIS CRAZY DIET AND

1872
01:03:23,680 --> 01:03:24,720
EXERCISE INTERVENTION JUST SLIDE

1873
01:03:24,720 --> 01:03:27,400
ALONG THE LINE AND LOSE THE

1874
01:03:27,400 --> 01:03:28,840
EXPECTED AMOUNT OF RESTING

1875
01:03:28,840 --> 01:03:29,560
METABOLIC RATE.

1876
01:03:29,560 --> 01:03:31,560
AND THE ANSWER WAS NO, THE OPEN

1877
01:03:31,560 --> 01:03:34,120
CIRCLES ARE AT THE END OF THIS

1878
01:03:34,120 --> 01:03:34,920
30-WEEK WEIGHT LOSS COMPETITION

1879
01:03:34,920 --> 01:03:36,880
YOU CAN SEE THAT EVERYBODY IS

1880
01:03:36,880 --> 01:03:39,480
FALLING WELL BELOW THE BEST FIT

1881
01:03:39,480 --> 01:03:41,960
LINE OF REGRESSION AT A MUCH

1882
01:03:41,960 --> 01:03:42,480
STEEPER SLOPE.

1883
01:03:42,480 --> 01:03:43,520
SO FOR EXAMPLE, THE PERSON THAT

1884
01:03:43,520 --> 01:03:46,640
I ILLUSTRATED BEFORE INSTEAD OF

1885
01:03:46,640 --> 01:03:48,160
FALLING ALONG THE LINE, HE FELL

1886
01:03:48,160 --> 01:03:49,320
TO THIS OPEN CIRCLE AT THE END

1887
01:03:49,320 --> 01:03:52,840
OF THE RED ARROW.

1888
01:03:52,840 --> 01:03:54,160
CLEARLY THERE'S A BIG

1889
01:03:54,160 --> 01:03:54,840
DISCREPANCY BETWEEN THE

1890
01:03:54,840 --> 01:03:56,320
PREDICTED AMOUNT OF DECREASE IN

1891
01:03:56,320 --> 01:03:58,040
RESTING ENERGY EXPENDITURE AND

1892
01:03:58,040 --> 01:03:59,400
THE AMOUNT THAT THEY ACTUALLY

1893
01:03:59,400 --> 01:04:00,000
EXPERIENCED.

1894
01:04:00,000 --> 01:04:01,880
A MUCH GREATER SLOWING OF

1895
01:04:01,880 --> 01:04:02,680
METABOLISM THAN WOULD BE

1896
01:04:02,680 --> 01:04:06,480
PREDICTED BASED ON THE BODY

1897
01:04:06,480 --> 01:04:07,040
COMPOSITION CHANGES ALONE.

1898
01:04:07,040 --> 01:04:09,600
SO WHAT WE CALL THAT PROCESS AND

1899
01:04:09,600 --> 01:04:10,280
MANY OTHER PEOPLE HAVE CALLED

1900
01:04:10,280 --> 01:04:13,640
THIS IS THE METABOLIC ADAPTATION

1901
01:04:13,640 --> 01:04:16,360
THAT'S HAPPENING AS A RESULT OF

1902
01:04:16,360 --> 01:04:17,800
THEIR WEIGHT LOSS.

1903
01:04:17,800 --> 01:04:19,720
IT'S THE GREATER THAN EXPECTED

1904
01:04:19,720 --> 01:04:21,360
SLOWING OF METABOLISM AS PEOPLE

1905
01:04:21,360 --> 01:04:24,320
LOSE THEIR WEIGHT.

1906
01:04:24,320 --> 01:04:25,520
LOSE WEIGHT AS A RESULT OF THIS

1907
01:04:25,520 --> 01:04:27,960
DIET INTERVENTION.

1908
01:04:27,960 --> 01:04:29,120
NOW, ONE OF THE PREDICTIONS

1909
01:04:29,120 --> 01:04:30,040
WOULD BE, IS THAT BECAUSE THESE

1910
01:04:30,040 --> 01:04:31,800
PEOPLE ARE NOW BURNING SO MANY

1911
01:04:31,800 --> 01:04:34,400
FEWER CALORIES THAN WOULD BE

1912
01:04:34,400 --> 01:04:36,760
EXPECTED FOR THEIR LOSS OF BODY

1913
01:04:36,760 --> 01:04:39,520
WEIGHT, THAT PERHAPS PEOPLE WHO

1914
01:04:39,520 --> 01:04:41,120
HAD THE GREATEST SLOWING OF

1915
01:04:41,120 --> 01:04:42,400
METABOLISM WOULD BE EXPECTED TO

1916
01:04:42,400 --> 01:04:43,680
REGAIN THE MOST AMOUNT OF

1917
01:04:43,680 --> 01:04:44,040
WEIGHT.

1918
01:04:44,040 --> 01:04:45,440
AFTER ALL, THEY'RE BURNING SO

1919
01:04:45,440 --> 01:04:48,680
MANY FEWER CALORIES THAT THEY

1920
01:04:48,680 --> 01:04:51,600
WOULD BE EXPECTED TO INCREASE

1921
01:04:51,600 --> 01:04:54,320
THEIR WEIGHT MORE THAN THOSE WHO

1922
01:04:54,320 --> 01:04:56,760
MIGHT HAVE HAD A MUCH LETTER

1923
01:04:56,760 --> 01:04:57,240
METABOLIC ADAPTATION.

1924
01:04:57,240 --> 01:04:58,720
YOU CAN SEE IN THE DATA OF THE

1925
01:04:58,720 --> 01:04:59,560
INDIVIDUAL DATA POINTS HERE,

1926
01:04:59,560 --> 01:05:01,960
THERE IS A RANGE, SO WE COULD

1927
01:05:01,960 --> 01:05:03,360
TEST THAT HYPOTHESIS AND IT WAS,

1928
01:05:03,360 --> 01:05:04,960
IN FACT, AN ASSUMPTION FOR A

1929
01:05:04,960 --> 01:05:05,440
VERY LONG TIME.

1930
01:05:05,440 --> 01:05:08,800
AND SO WE BROUGHT BACK THE

1931
01:05:08,800 --> 01:05:09,400
CONTESTANTS OF THAT SEASON OF

1932
01:05:09,400 --> 01:05:11,840
THE BIGGEST LOSER TO THE NIH

1933
01:05:11,840 --> 01:05:13,760
CLINICAL CENTER TO MEASURE THEIR

1934
01:05:13,760 --> 01:05:15,520
METABOLIC RATE AND BODY

1935
01:05:15,520 --> 01:05:16,240
COMPOSITION AGAIN.

1936
01:05:16,240 --> 01:05:19,800
THIS IS DANNY CAHILL SIX YEARS

1937
01:05:19,800 --> 01:05:22,600
AFTER THE BIGGEST LOSER

1938
01:05:22,600 --> 01:05:22,880
COMPETITION.

1939
01:05:22,880 --> 01:05:24,200
AND IT WAS A FEATURE OF A "NEW

1940
01:05:24,200 --> 01:05:25,160
YORK TIMES" ARTICLE.

1941
01:05:25,160 --> 01:05:28,320
YOU CAN SEE JUST VISUALLY HE'S

1942
01:05:28,320 --> 01:05:29,320
CLEARLY REGAINED SOME OF HIS

1943
01:05:29,320 --> 01:05:29,720
LOST WEIGHT.

1944
01:05:29,720 --> 01:05:30,920
I'LL SHOW YOU SOME OTHER PHOTOS

1945
01:05:30,920 --> 01:05:32,920
OF SOME OF THE OTHER CONTESTANTS

1946
01:05:32,920 --> 01:05:34,960
BEFORE AND AFTER THE BIGGEST

1947
01:05:34,960 --> 01:05:35,480
LOSER COMPETITION.

1948
01:05:35,480 --> 01:05:38,960
THIS IS DENA ON THE LEFT, BEFORE

1949
01:05:38,960 --> 01:05:40,400
THE COMPETITION BEGAN, ON THE

1950
01:05:40,400 --> 01:05:42,000
RIGHT, AFTER 30 WEEKS, AND THEN

1951
01:05:42,000 --> 01:05:43,880
SIX YEARS LATER.

1952
01:05:43,880 --> 01:05:46,440
THIS IS SHAWN, BEFORE ON THE

1953
01:05:46,440 --> 01:05:48,640
LEFT, AFTER ON THE RIGHT, AND

1954
01:05:48,640 --> 01:05:51,000
THEN SIX YEARS LATER.

1955
01:05:51,000 --> 01:05:53,640
THIS IS ABBY BEFORE ON THE LEFT,

1956
01:05:53,640 --> 01:05:54,960
AFTER ON THE RIGHT.

1957
01:05:54,960 --> 01:05:57,000
AND THEN SIX YEARS LATER.

1958
01:05:57,000 --> 01:05:59,520
AND TRACY, BEFORE ON THE LEFT,

1959
01:05:59,520 --> 01:06:01,160
AFTER ON THE RIGHT, AND THEN SIX

1960
01:06:01,160 --> 01:06:02,240
YEARS LATER.

1961
01:06:02,240 --> 01:06:04,240
I THINK WHAT YOU CAN SEE IS JUST

1962
01:06:04,240 --> 01:06:06,040
VISUALLY, THERE IS QUITE A BIT

1963
01:06:06,040 --> 01:06:07,720
OF VARIABILITY IN THE AMOUNT OF

1964
01:06:07,720 --> 01:06:09,760
WEIGHT THAT WAS REGAINED.

1965
01:06:09,760 --> 01:06:12,240
HERE ARE ALL THE DATA POINTS.

1966
01:06:12,240 --> 01:06:13,800
AT 30 WEEKS, AT THE END OF THE

1967
01:06:13,800 --> 01:06:15,080
COMPETITION, LIKE I MENTIONED

1968
01:06:15,080 --> 01:06:16,600
BEFORE, THE GREY LINE IS SAYING

1969
01:06:16,600 --> 01:06:20,200
THAT ON AVERAGE, PEOPLE HAD LOST

1970
01:06:20,200 --> 01:06:20,440
60-KILOS.

1971
01:06:20,440 --> 01:06:22,200
AND SIX YEARS LATER, THEY HAD,

1972
01:06:22,200 --> 01:06:23,960
ON AVERAGE, REGAINED ABOUT TWO

1973
01:06:23,960 --> 01:06:25,080
THIRDS OF THEIR LOST WEIGHT, BUT

1974
01:06:25,080 --> 01:06:26,880
THERE WAS QUITE A BIT OF

1975
01:06:26,880 --> 01:06:27,200
VARIABILITY.

1976
01:06:27,200 --> 01:06:28,840
ONE PERSON EVEN CONTINUED TO

1977
01:06:28,840 --> 01:06:31,880
LOSE EVEN MORE WEIGHT AFTER SIX

1978
01:06:31,880 --> 01:06:32,480
YEARS.

1979
01:06:32,480 --> 01:06:35,240
AND THIS WAS PORTRAYED IN THE

1980
01:06:35,240 --> 01:06:35,840
"NEW YORK TIMES" ARTICLE AND A

1981
01:06:35,840 --> 01:06:37,480
LOT OF THE SUBSEQUENT COVERAGE

1982
01:06:37,480 --> 01:06:39,320
AS A BIG FAILURE, RIGHT, THAT

1983
01:06:39,320 --> 01:06:41,480
THESE FOLKS HAD REGAINED SO MUCH

1984
01:06:41,480 --> 01:06:43,760
WEIGHT AFTER SIX YEARS.

1985
01:06:43,760 --> 01:06:44,960
BUT ONE OF THE THINGS I'D LIKE

1986
01:06:44,960 --> 01:06:47,040
TO POINT OUT IS THAT AFTER SIX

1987
01:06:47,040 --> 01:06:48,360
YEARS, THEY WERE STILL

1988
01:06:48,360 --> 01:06:50,160
MAINTAINING AN AVERAGE OF ABOUT

1989
01:06:50,160 --> 01:06:51,520
13% WEIGHT LOSS.

1990
01:06:51,520 --> 01:06:53,720
WHICH IS PRETTY DARN GOOD.

1991
01:06:53,720 --> 01:06:57,400
THAT'S ACTUALLY PRETTY GOOD

1992
01:06:57,400 --> 01:07:00,640
LONG-TERM EFFECT OF THIS KIND OF

1993
01:07:00,640 --> 01:07:01,880
CRAZY AND UNSUSTAINABLE

1994
01:07:01,880 --> 01:07:02,640
INTERVENTION THAT OCCURRED OVER

1995
01:07:02,640 --> 01:07:04,080
THE COURSE OF THE ACTUAL

1996
01:07:04,080 --> 01:07:04,640
COMPETITION.

1997
01:07:04,640 --> 01:07:06,040
BUT THERE WAS SOME VARIABILITY

1998
01:07:06,040 --> 01:07:07,040
AND ONE OF THE QUESTIONS THAT WE

1999
01:07:07,040 --> 01:07:10,440
WANTED TO ANSWER WAS, DID THE

2000
01:07:10,440 --> 01:07:12,880
PEOPLE WHO HAD REGAINED THE MOST

2001
01:07:12,880 --> 01:07:14,080
WEIGHT, WERE THEY THE ONES WHO

2002
01:07:14,080 --> 01:07:15,680
HAD EXPERIENCED THE GREATEST

2003
01:07:15,680 --> 01:07:17,360
SLOWING AT THE END OF THE

2004
01:07:17,360 --> 01:07:18,960
30-WEEK COMPETITION, THAT WAS

2005
01:07:18,960 --> 01:07:20,800
THE ASSUMPTION AND HAD BEEN THE

2006
01:07:20,800 --> 01:07:22,720
ASSUMPTION FOR QUITE SOME TIME.

2007
01:07:22,720 --> 01:07:23,800
AND IN FACT, THERE WAS NO

2008
01:07:23,800 --> 01:07:25,440
SIGNIFICANT RELATIONSHIP

2009
01:07:25,440 --> 01:07:25,800
WHATSOEVER.

2010
01:07:25,800 --> 01:07:27,840
SO THE PEOPLE HAD THE GREATEST

2011
01:07:27,840 --> 01:07:28,600
METABOLIC SLOWING AT THE END OF

2012
01:07:28,600 --> 01:07:30,000
THE COMPETITION WERE -- THERE

2013
01:07:30,000 --> 01:07:31,120
WAS NO RELATIONSHIP TO THE

2014
01:07:31,120 --> 01:07:33,640
AMOUNT OF WEIGHT THAT THEY

2015
01:07:33,640 --> 01:07:35,880
REGAINED AFTER SIX YEARS.

2016
01:07:35,880 --> 01:07:38,800
SO WHAT DID PREDICT THE WEIGHT

2017
01:07:38,800 --> 01:07:39,320
REGAIN?

2018
01:07:39,320 --> 01:07:40,440
WHAT WAS THE GREATEST

2019
01:07:40,440 --> 01:07:40,960
CONTRIBUTOR?

2020
01:07:40,960 --> 01:07:42,200
ONE OF THE THINGS THAT WE DID

2021
01:07:42,200 --> 01:07:45,640
WAS WE SPLIT THE GROUPS UP INTO

2022
01:07:45,640 --> 01:07:47,840
THE MEDIAN OF THOSE WHO HAD LOST

2023
01:07:47,840 --> 01:07:49,840
MORE THAN 13% OF WEIGHT LOSS AT

2024
01:07:49,840 --> 01:07:51,360
THE END OF THE SIX-YEAR PERIOD

2025
01:07:51,360 --> 01:07:53,240
AND THOSE THAT WHO LOST LESS

2026
01:07:53,240 --> 01:07:53,800
THAN 13%.

2027
01:07:53,800 --> 01:07:57,120
THE MEAN VALUES IN THOSE TWO

2028
01:07:57,120 --> 01:07:58,840
GROUPS WAS -- ONE GROUP HAD

2029
01:07:58,840 --> 01:08:00,000
MAINTAINED 25% WEIGHT LOSS AND

2030
01:08:00,000 --> 01:08:01,320
THE OTHER HAD REGAINED BASICALLY

2031
01:08:01,320 --> 01:08:04,400
ALL OF THEIR BODY WEIGHT.

2032
01:08:04,400 --> 01:08:06,040
AND WE HAD THESE OBJECTIVE

2033
01:08:06,040 --> 01:08:06,880
MEASUREMENTS OF ENERGY INTAKE

2034
01:08:06,880 --> 01:08:08,680
AND PHYSICAL ACTIVITY ENERGY

2035
01:08:08,680 --> 01:08:09,280
EXPENDITURE.

2036
01:08:09,280 --> 01:08:10,960
AND IN THESE TWO GROUPS, THERE

2037
01:08:10,960 --> 01:08:12,840
WAS NO SIGNIFICANT DIFFERENCE IN

2038
01:08:12,840 --> 01:08:14,320
THE ENERGY INTAKE BETWEEN THE

2039
01:08:14,320 --> 01:08:17,120
GROUPS, THE CHANGES FROM THE

2040
01:08:17,120 --> 01:08:18,520
BASELINE COMPARED TO SIX YEARS,

2041
01:08:18,520 --> 01:08:20,880
BUT THERE WAS HUGE DIFFERENCES

2042
01:08:20,880 --> 01:08:23,160
IN THE ENERGY EXPENDITURE WITH

2043
01:08:23,160 --> 01:08:24,600
ONE GROUP INCREASING THEIR

2044
01:08:24,600 --> 01:08:25,800
ENERGY EXPENDITURE BY MORE THAN

2045
01:08:25,800 --> 01:08:28,720
150% COMPARED TO BASELINE, IN

2046
01:08:28,720 --> 01:08:30,400
TERMS OF THEIR PHYSICAL

2047
01:08:30,400 --> 01:08:32,120
ACTIVITY, AND THE OTHER GROUP

2048
01:08:32,120 --> 01:08:34,840
BASICALLY HAVING A VERY MODEST

2049
01:08:34,840 --> 01:08:37,280
INCREASE IN PHYSICAL ACTIVITY.

2050
01:08:37,280 --> 01:08:38,880
CONTINUOUSLY, THE DATA LOOK LIKE

2051
01:08:38,880 --> 01:08:39,640
THIS.

2052
01:08:39,640 --> 01:08:41,520
CLEARLY THE FOLKS WHO HAD

2053
01:08:41,520 --> 01:08:44,080
INCREASED THEIR PHYSICAL

2054
01:08:44,080 --> 01:08:45,440
ACTIVITY, ENERGY EXPENDITURE THE

2055
01:08:45,440 --> 01:08:46,920
MOST MAINTAINED THE MOST WEIGHT

2056
01:08:46,920 --> 01:08:47,120
LOSS.

2057
01:08:47,120 --> 01:08:48,600
AND THIS IS SOMETHING THAT HAS

2058
01:08:48,600 --> 01:08:50,640
BEEN OBSERVED IN OTHER

2059
01:08:50,640 --> 01:08:53,840
REGISTRIES OF PEOPLE WHO HAD

2060
01:08:53,840 --> 01:08:54,640
MAINTAINED SUBSTANTIAL AMOUNTS

2061
01:08:54,640 --> 01:08:55,360
OF WEIGHT LOSS.

2062
01:08:55,360 --> 01:08:56,680
ONE OF THE COMMON FACTORS IS

2063
01:08:56,680 --> 01:08:58,720
THAT THEY BECOME RELATIVELY

2064
01:08:58,720 --> 01:09:01,800
PHYSICALLY ACTIVE IN ORDER TO

2065
01:09:01,800 --> 01:09:03,960
MAINTAIN THAT WEIGHT LOSS.

2066
01:09:03,960 --> 01:09:05,320
SO THAT'S DEPICTED HERE IN THESE

2067
01:09:05,320 --> 01:09:06,320
LONGITUDINAL STUDIES OF THE

2068
01:09:06,320 --> 01:09:08,360
BIGGEST LOSER PARTICIPANTS.

2069
01:09:08,360 --> 01:09:09,240
SO SOMETHING ELSE THAT WAS

2070
01:09:09,240 --> 01:09:11,640
REALLY INTERESTING WAS THAT

2071
01:09:11,640 --> 01:09:14,880
DESPITE REGAINING THE BODY

2072
01:09:14,880 --> 01:09:16,400
WEIGHT, TWO THIRDS OF THE BODY

2073
01:09:16,400 --> 01:09:18,120
WEIGHT ON AVERAGE RESTING ENERGY

2074
01:09:18,120 --> 01:09:19,280
EXPENDITURE OR RESTING METABOLIC

2075
01:09:19,280 --> 01:09:21,440
RATE AS PLOTTED HERE IS

2076
01:09:21,440 --> 01:09:26,120
BASICALLY UNCHANGED.

2077
01:09:26,120 --> 01:09:27,280
SUGGESTING THAT THIS METABOLIC

2078
01:09:27,280 --> 01:09:29,400
SLOWING THAT HAD TAKEN PLACE

2079
01:09:29,400 --> 01:09:31,040
OVER THE COURSE OF THE BIGGEST

2080
01:09:31,040 --> 01:09:33,120
LOSER COMPETITION WAS MAINTAINED

2081
01:09:33,120 --> 01:09:33,840
SIX YEARS LATER.

2082
01:09:33,840 --> 01:09:35,880
AND IN FACT, ONE OF THE THINGS

2083
01:09:35,880 --> 01:09:37,800
THAT WAS VERY INTERESTING WAS

2084
01:09:37,800 --> 01:09:40,360
THAT DESPITE WHAT WE MIGHT HAVE

2085
01:09:40,360 --> 01:09:41,840
EXPECTED, THE AMOUNT OF

2086
01:09:41,840 --> 01:09:45,520
METABOLIC SLOWING AT SIX YEARS

2087
01:09:45,520 --> 01:09:47,320
WAS POSITIVELY RELATED TO THE

2088
01:09:47,320 --> 01:09:48,880
AMOUNT OF WEIGHT REGAIN SUCH

2089
01:09:48,880 --> 01:09:51,520
THAT THOSE WHO EXPERIENCED AT

2090
01:09:51,520 --> 01:09:53,760
SIX YEARS THE GREATEST AMOUNT OF

2091
01:09:53,760 --> 01:09:54,920
METABOLIC SLOWING WERE THE ONES

2092
01:09:54,920 --> 01:09:56,480
WHO HAD BEEN MOST SUCCESSFUL,

2093
01:09:56,480 --> 01:09:58,160
NOT LEAST SUCCESSFUL, MOST

2094
01:09:58,160 --> 01:10:00,800
SUCCESSFUL AT MAINTAINING THEIR

2095
01:10:00,800 --> 01:10:02,160
WEIGHT LOSS AT THE SAME TIME

2096
01:10:02,160 --> 01:10:02,360
POINT.

2097
01:10:02,360 --> 01:10:03,800
SO HOW DO WE MAKE SENSE OF THIS?

2098
01:10:03,800 --> 01:10:05,160
AFTER ALL, THEY'RE THE ONES WHO

2099
01:10:05,160 --> 01:10:06,800
HAVE THE GREATEST SLOWING OF

2100
01:10:06,800 --> 01:10:07,200
METABOLISM.

2101
01:10:07,200 --> 01:10:09,120
HOW CAN THEY BE THE ONES WHO

2102
01:10:09,120 --> 01:10:11,800
HAVE BEEN MOST SUCCESSFUL AND

2103
01:10:11,800 --> 01:10:12,680
KEEPING THE WEIGHT OFFER?

2104
01:10:12,680 --> 01:10:13,880
ONE WAY TO KIND OF THINK ABOUT

2105
01:10:13,880 --> 01:10:16,440
IT IS THIS RESISTANCE TO WEIGHT

2106
01:10:16,440 --> 01:10:18,920
LOSS AND INTERVENTIONS IS KIND

2107
01:10:18,920 --> 01:10:22,040
OF LIKE THE TENSION ON A SPRING.

2108
01:10:22,040 --> 01:10:23,840
AND IF THE INTERVENTION IS THE

2109
01:10:23,840 --> 01:10:26,040
AMOUNT THAT YOU'RE PULLING ON

2110
01:10:26,040 --> 01:10:27,320
THE SPRING, AND IF YOU'RE NOT

2111
01:10:27,320 --> 01:10:28,200
PULLING ON THE SPRING, YOU'RE

2112
01:10:28,200 --> 01:10:29,120
NOT GOING TO LOSE ANY WEIGHT.

2113
01:10:29,120 --> 01:10:31,120
SO THE TENSION ON THE SPRING IS

2114
01:10:31,120 --> 01:10:31,320
ZERO.

2115
01:10:31,320 --> 01:10:34,480
WHEREAS IF YOU THEN PULL ON THE

2116
01:10:34,480 --> 01:10:36,800
SPRING BY CUTTING CALORIES IN

2117
01:10:36,800 --> 01:10:37,760
YOUR DIET OR INCREASING YOUR

2118
01:10:37,760 --> 01:10:39,400
PHYSICAL ACTIVITY, YOU WILL LOSE

2119
01:10:39,400 --> 01:10:41,320
WEIGHT, BUT THERE WILL BE A

2120
01:10:41,320 --> 01:10:43,200
TENSION ON THE SPRING, IN

2121
01:10:43,200 --> 01:10:44,680
PROPORTION TO THE AMOUNT THAT

2122
01:10:44,680 --> 01:10:45,800
YOU'RE PULLING ON IT.

2123
01:10:45,800 --> 01:10:48,800
GREATER THAT YOU PULL ON IT, THE

2124
01:10:48,800 --> 01:10:50,440
GREATER THE RESISTANCE OR THE

2125
01:10:50,440 --> 01:10:51,120
TENSION ON THE SPRING.

2126
01:10:51,120 --> 01:10:54,400
SO THAT WOULD BE WHY YOU MIGHT

2127
01:10:54,400 --> 01:10:55,720
HAVE THIS RELATIONSHIP I SHOWED

2128
01:10:55,720 --> 01:10:57,080
YOU ON THE PREVIOUS CURVE.

2129
01:10:57,080 --> 01:11:00,600
THOSE WHO HAD THE GREATEST

2130
01:11:00,600 --> 01:11:01,720
METABOLIC ADAPTATION HAD THE

2131
01:11:01,720 --> 01:11:02,440
GREATEST TENSION ON THE SPRING

2132
01:11:02,440 --> 01:11:04,080
BECAUSE THEY WERE RESISTING A

2133
01:11:04,080 --> 01:11:06,760
GREATER INTENSITY OF

2134
01:11:06,760 --> 01:11:07,160
INTERVENTION.

2135
01:11:07,160 --> 01:11:08,240
AND IN PARTICULAR, PHYSICAL

2136
01:11:08,240 --> 01:11:10,960
ACTIVITY IN THE CASE OF THE

2137
01:11:10,960 --> 01:11:15,920
BIGGEST LOSERS.

2138
01:11:15,920 --> 01:11:18,680
LET'S MOVE ON AND TALK ABOUT

2139
01:11:18,680 --> 01:11:23,840
MAYBE NOT SUCH AN EXTREME WEIGHT

2140
01:11:23,840 --> 01:11:26,160
LOSS, I DON'T HAVE TIME TO GO

2141
01:11:26,160 --> 01:11:27,280
INTO THE DETAILS BUT IN THIS

2142
01:11:27,280 --> 01:11:29,880
PAPER IN 2016, WE QUANTIFIED ON

2143
01:11:29,880 --> 01:11:32,200
AVERAGE WHAT THE RELATIVE

2144
01:11:32,200 --> 01:11:33,360
FEEDBACK CONTROL STRENGTH THAT

2145
01:11:33,360 --> 01:11:35,120
RESISTS WEIGHT LOSS IS ON BOTH

2146
01:11:35,120 --> 01:11:38,720
THE APPETITE SIDE AND THE ENERGY

2147
01:11:38,720 --> 01:11:40,240
EXPENDITURE SIDE OF THE ENERGY

2148
01:11:40,240 --> 01:11:41,320
BALANCE EQUATION, AND WHAT WE

2149
01:11:41,320 --> 01:11:42,680
COMPUTED WAS THAT ON THE CALORIE

2150
01:11:42,680 --> 01:11:45,160
OUTPUT SIDE, FOR EVERY KILO OF

2151
01:11:45,160 --> 01:11:47,080
BODY WEIGHT THAT'S LOST, ENERGY

2152
01:11:47,080 --> 01:11:49,560
EXPENDITURE GOES DOWN BY ABOUT

2153
01:11:49,560 --> 01:11:50,800
25 KILOCALORIES PER DAY.

2154
01:11:50,800 --> 01:11:53,160
SO IF YOU LOSE ABOUT 22 POUNDS

2155
01:11:53,160 --> 01:11:56,200
OR 10-KILOS, YOU WILL BE BURNING

2156
01:11:56,200 --> 01:11:57,480
ROUGHLY 250-CALORIES PER DAY

2157
01:11:57,480 --> 01:11:59,080
LESS THAN YOU WERE TO BEGIN

2158
01:11:59,080 --> 01:12:00,080
WITH.

2159
01:12:00,080 --> 01:12:02,040
ON THE APPETITE SIDE, THE

2160
01:12:02,040 --> 01:12:02,880
FEEDBACK CONTROL STRENGTH IS

2161
01:12:02,880 --> 01:12:04,560
ACTUALLY MUCH STRONGER.

2162
01:12:04,560 --> 01:12:06,440
ACCORDING TO OUR INITIAL

2163
01:12:06,440 --> 01:12:07,440
ESTIMATES.

2164
01:12:07,440 --> 01:12:09,120
SUCH THAT WILL FOR EVERY KILO OF

2165
01:12:09,120 --> 01:12:11,000
WEIGHT THAT'S LOST, YOUR

2166
01:12:11,000 --> 01:12:12,400
APPETITE INCREASES ABOVE

2167
01:12:12,400 --> 01:12:15,040
BASELINE BY ABOUT 95 KILL

2168
01:12:15,040 --> 01:12:17,000
CALORIES PER DAY, AND I'D LIKE

2169
01:12:17,000 --> 01:12:18,760
TO TRACE OUT WHAT THAT MEANS

2170
01:12:18,760 --> 01:12:19,840
PRACTICALLY FOR PEOPLE WHO ARE

2171
01:12:19,840 --> 01:12:22,160
ENGAGING IN CALORIE RESTRICTION

2172
01:12:22,160 --> 01:12:24,680
FOR WEIGHT LOSS.

2173
01:12:24,680 --> 01:12:26,560
JUST TO KIND OF PLOT WHAT THOSE

2174
01:12:26,560 --> 01:12:27,920
TWO SORT OF CURVES LOOK LIKE AS

2175
01:12:27,920 --> 01:12:30,480
A FUNCTION OF BODY WEIGHT, WE'RE

2176
01:12:30,480 --> 01:12:31,560
ASSUMING THEY'RE LINEAR HERE,

2177
01:12:31,560 --> 01:12:32,880
BUT YOU CAN SEE THAT THE

2178
01:12:32,880 --> 01:12:34,960
APPETITE CURVE HAS A SLOPE OF

2179
01:12:34,960 --> 01:12:37,120
MINUS 95 KILL CALORIES PER DAY

2180
01:12:37,120 --> 01:12:38,880
PER KILO OF BODY WEIGHT CHANGE

2181
01:12:38,880 --> 01:12:41,840
AND THE EXPENDITURE IS ABOUT

2182
01:12:41,840 --> 01:12:45,240
25 KILOCALORIES PER DAY.

2183
01:12:45,240 --> 01:12:46,760
WHEN INTAKE AND EXPENDITURE ARE

2184
01:12:46,760 --> 01:12:48,120
EQUAL, YOUR BODY IS IN BALANCE

2185
01:12:48,120 --> 01:12:49,640
AND YOU WILL MAINTAIN A STABLE

2186
01:12:49,640 --> 01:12:53,640
BODY WEIGHT, IN THIS CASE, ABOUT

2187
01:12:53,640 --> 01:12:56,240
85 KILOGRAMS EATING ABOUT

2188
01:12:56,240 --> 01:12:56,960
3100 KILOCALORIES PER DAY ON

2189
01:12:56,960 --> 01:13:01,880
THIS CURVE.

2190
01:13:01,880 --> 01:13:03,120
SO WHAT HAPPENS WHEN YOU TRY TO

2191
01:13:03,120 --> 01:13:04,640
CUT CALORIES IN YOUR DIET?

2192
01:13:04,640 --> 01:13:06,560
ONE WAY TO THINK ABOUT IT IS IF

2193
01:13:06,560 --> 01:13:07,880
YOU HAVEN'T CHANGED THE

2194
01:13:07,880 --> 01:13:09,240
UNDERLYING BIOLOGY OF THE

2195
01:13:09,240 --> 01:13:11,840
SYSTEM, YOU'RE ESSENTIALLY

2196
01:13:11,840 --> 01:13:12,680
SEPARATING INTAKE FROM YOUR

2197
01:13:12,680 --> 01:13:13,280
APPETITE.

2198
01:13:13,280 --> 01:13:14,720
SO YOUR APPETITE STAYS WHERE IT

2199
01:13:14,720 --> 01:13:16,120
WAS IN THE PREVIOUS CURVE,

2200
01:13:16,120 --> 01:13:17,520
INDICATED BY A DASHED LINE,

2201
01:13:17,520 --> 01:13:18,520
INTAKE HAS BEEN SHIFTED

2202
01:13:18,520 --> 01:13:20,080
DOWNWARDS, IN THIS CASE, TO A

2203
01:13:20,080 --> 01:13:23,920
NEW VALUE OF ABOUT 2500-CALORIES

2204
01:13:23,920 --> 01:13:25,760
PER DAY IN THIS PERSON WHO IS

2205
01:13:25,760 --> 01:13:27,720
STARTING OFF AT 85-KILOS.

2206
01:13:27,720 --> 01:13:29,200
AND THAT SEPARATION OF INTAKE

2207
01:13:29,200 --> 01:13:31,400
FROM APPETITE WOULD THEN PREDICT

2208
01:13:31,400 --> 01:13:32,720
AS THIS PERSON GOES INTO WHAT'S

2209
01:13:32,720 --> 01:13:34,160
CALLED A NEGATIVE ENERGY

2210
01:13:34,160 --> 01:13:35,240
BALANCE, THEY'RE BURNING MORE

2211
01:13:35,240 --> 01:13:37,560
THAN THEY'RE EATING, AND,

2212
01:13:37,560 --> 01:13:38,520
THEREFORE, THEY WOULD HAVE A

2213
01:13:38,520 --> 01:13:39,840
CERTAIN AMOUNT OF HUNGER AND

2214
01:13:39,840 --> 01:13:42,400
EFFORT ASSOCIATED WITH

2215
01:13:42,400 --> 01:13:46,400
MAINTAINING THIS CUT IN CALORIES

2216
01:13:46,400 --> 01:13:48,120
BUT THEY WOULD SLIDE UPWARDS THE

2217
01:13:48,120 --> 01:13:50,160
INTAKE LINE UNTIL THEY REACH A

2218
01:13:50,160 --> 01:13:53,720
NEW EQUILIBRIUM WHERE ENERGY

2219
01:13:53,720 --> 01:13:56,160
INTAKE AND EXPEND TEURL ARE IN

2220
01:13:56,160 --> 01:13:59,840
BALANCE AND REACH THIS NEW

2221
01:13:59,840 --> 01:14:02,200
STEADY STATE OF BODY WEIGHT --

2222
01:14:02,200 --> 01:14:03,920
THAT IT TAKES TO SEPARATE THAT

2223
01:14:03,920 --> 01:14:05,000
INTAKE CURVE FROM THE APPETITE

2224
01:14:05,000 --> 01:14:05,320
CURVE.

2225
01:14:05,320 --> 01:14:06,360
SO THE PREDICTION IS THAT WHEN

2226
01:14:06,360 --> 01:14:08,720
PEOPLE GO ON A

2227
01:14:08,720 --> 01:14:09,560
CALORIE-RESTRICTED DIET THAT

2228
01:14:09,560 --> 01:14:10,960
THEY WOULD INITIALLY CUT THEIR

2229
01:14:10,960 --> 01:14:15,160
CALORIES QUITE A LOT, THAT'S

2230
01:14:15,160 --> 01:14:17,880
THAT INITIAL REDUCTION, AND THAT

2231
01:14:17,880 --> 01:14:20,520
THEIR ENERGY EXPENDITURE WOULD

2232
01:14:20,520 --> 01:14:22,000
GO DOWN AND SLIDE UP THE INTAKE

2233
01:14:22,000 --> 01:14:22,200
CURVE.

2234
01:14:22,200 --> 01:14:23,360
SO DOES THAT REALLY HAPPEN?

2235
01:14:23,360 --> 01:14:25,640
SO WE HAVE SOME REALLY

2236
01:14:25,640 --> 01:14:27,640
REMARKABLE DATA, TWO-YEAR DATA

2237
01:14:27,640 --> 01:14:29,680
FROM A 25% CALORIE RESTRICTION

2238
01:14:29,680 --> 01:14:31,400
INTERVENTION, SOMETHING CALLED A

2239
01:14:31,400 --> 01:14:32,760
CALORIE STUDY THAT WAS SUPPORTED

2240
01:14:32,760 --> 01:14:35,200
BY THE NATIONAL INSTITUTES ON

2241
01:14:35,200 --> 01:14:36,440
AGING, AND HERE'S THE DATA FOR

2242
01:14:36,440 --> 01:14:38,880
THE BODY WEIGHT AND BODY FAT

2243
01:14:38,880 --> 01:14:40,360
CHANGES IN THE PARTICIPANTS OF

2244
01:14:40,360 --> 01:14:41,320
THE CALORIE DATA.

2245
01:14:41,320 --> 01:14:45,080
AND THE GOAL HERE OF THE CALORIE

2246
01:14:45,080 --> 01:14:46,440
STUDY WAS TO CUT ENERGY INTAKE

2247
01:14:46,440 --> 01:14:49,720
BY A CONSTANT 25% AND KEEP IT AT

2248
01:14:49,720 --> 01:14:52,480
THAT LOWER LEVEL FOR THE ENTIRE

2249
01:14:52,480 --> 01:14:53,320
DURATION OF THE STUDY.

2250
01:14:53,320 --> 01:14:54,640
AND SO FIRST THING TO NOTE IS

2251
01:14:54,640 --> 01:14:56,160
THAT THESE PEOPLE DIDN'T

2252
01:14:56,160 --> 01:14:57,600
DISAPPEAR AFTER TWO YEARS, THEY

2253
01:14:57,600 --> 01:14:59,680
PLATEAUED THEIR BODY WEIGHT

2254
01:14:59,680 --> 01:15:01,040
AFTER ABOUT 12 MONTHS.

2255
01:15:01,040 --> 01:15:03,000
AND LOST MOST OF THEIR WEIGHT

2256
01:15:03,000 --> 01:15:04,760
LOSS COMING FROM BODY FAT

2257
01:15:04,760 --> 01:15:05,360
CHANGE, AGAIN, THE SIMULATIONS

2258
01:15:05,360 --> 01:15:06,640
ARE THE CURVES AND THE DATA

2259
01:15:06,640 --> 01:15:09,200
POINTS ARE THE CIRCLES AND

2260
01:15:09,200 --> 01:15:10,600
TRIANGLES RESPECTIVELY FOR

2261
01:15:10,600 --> 01:15:12,200
EVALUATING BODY FAT.

2262
01:15:12,200 --> 01:15:15,080
BUT UNDERLYING THIS, THESE

2263
01:15:15,080 --> 01:15:16,040
INVESTIGATORS WENT TO GREAT

2264
01:15:16,040 --> 01:15:19,240
EXPENSE TO USE REPEATED MEASURES

2265
01:15:19,240 --> 01:15:21,880
OF DOUBLY LABELED WATER AND BODY

2266
01:15:21,880 --> 01:15:24,360
COMPOSITION CHANGES TO INFER

2267
01:15:24,360 --> 01:15:26,160
WHAT THE ENERGY INTAKE CHANGES

2268
01:15:26,160 --> 01:15:28,480
MUST HAVE BEEN, AND INDEED, WHAT

2269
01:15:28,480 --> 01:15:30,200
THEY FOUND WAS THAT ENERGY

2270
01:15:30,200 --> 01:15:33,120
INTAKE WAS INITIALLY REDUCED AND

2271
01:15:33,120 --> 01:15:35,000
DESPITE THIS CONSTANT INTENSITY

2272
01:15:35,000 --> 01:15:36,640
INTERVENTION, SEEING

2273
01:15:36,640 --> 01:15:37,840
NUTRITIONISTS ON A REGULAR BASIS

2274
01:15:37,840 --> 01:15:41,240
TO TRY TO KEEP A 25% CALORIE

2275
01:15:41,240 --> 01:15:44,160
CUT, YOU CAN SEE THAT THE ENERGY

2276
01:15:44,160 --> 01:15:45,640
INTAKE CURVE CREEPS UPWARDS

2277
01:15:45,640 --> 01:15:48,320
AFTER THAT INITIAL 25% CALORIE

2278
01:15:48,320 --> 01:15:48,840
REDUCTION.

2279
01:15:48,840 --> 01:15:50,240
JUST EXACTLY ACCORDING TO WHAT

2280
01:15:50,240 --> 01:15:53,040
WAS PREDICTED BASED ON THAT

2281
01:15:53,040 --> 01:15:53,920
APPETITE MODEL I SHOWED YOU A

2282
01:15:53,920 --> 01:15:54,880
MOMENT AGO.

2283
01:15:54,880 --> 01:15:56,440
ENERGY EXPENDITURE IN THE ORANGE

2284
01:15:56,440 --> 01:15:57,480
CURVE GOES DOWN AND SORT OF

2285
01:15:57,480 --> 01:15:59,080
STAYS DOWN, AND OF COURSE WHEN

2286
01:15:59,080 --> 01:16:00,520
THOSE TWO CURVES CROSS EACH

2287
01:16:00,520 --> 01:16:02,640
OTHER AT 12 MONTHS, THAT'S WHERE

2288
01:16:02,640 --> 01:16:04,360
THE PLATEAU IS.

2289
01:16:04,360 --> 01:16:06,760
AND SO YOU CAN KIND OF

2290
01:16:06,760 --> 01:16:08,360
REINTERPRET THIS AND PLOT THE

2291
01:16:08,360 --> 01:16:08,800
APPETITE.

2292
01:16:08,800 --> 01:16:10,120
I TOLD YOU THAT APPETITE

2293
01:16:10,120 --> 01:16:12,960
INCREASES BY ABOUT

2294
01:16:12,960 --> 01:16:14,880
95 KILOCALORIES PER DAY ABOVE

2295
01:16:14,880 --> 01:16:15,880
BASELINE, FOR EVERY KILOGRAM OF

2296
01:16:15,880 --> 01:16:17,520
WEIGHT THAT IS LOST, SO THAT'S

2297
01:16:17,520 --> 01:16:19,160
BASICALLY JUST THIS DASHED LINE

2298
01:16:19,160 --> 01:16:20,840
THAT I'M PLOTTING HERE BASED ON

2299
01:16:20,840 --> 01:16:22,440
THE OBSERVED BODY WEIGHT

2300
01:16:22,440 --> 01:16:22,840
CHANGES.

2301
01:16:22,840 --> 01:16:25,040
SO THE THING THAT I THINK IS

2302
01:16:25,040 --> 01:16:27,680
INTERESTING IS, AGAIN, ACCORDING

2303
01:16:27,680 --> 01:16:29,240
TO THE MODEL THAT WE PREDICTED

2304
01:16:29,240 --> 01:16:30,880
THAT THERE IS A PERSISTENT

2305
01:16:30,880 --> 01:16:32,440
DIFFERENCE BETWEEN THE SOLID

2306
01:16:32,440 --> 01:16:33,600
BLUE LINE WHICH IS WHAT THESE

2307
01:16:33,600 --> 01:16:35,480
FOLKS ARE DOING TO ACTUALLY CUT

2308
01:16:35,480 --> 01:16:37,320
THEIR CALORIES AND WHAT THEIR

2309
01:16:37,320 --> 01:16:38,800
BODY IS TELLING THEM THEY'D LIKE

2310
01:16:38,800 --> 01:16:39,920
TO BE EATING, WHICH IS THE

2311
01:16:39,920 --> 01:16:42,480
DASHED BLUE LINE, THAT FOR

2312
01:16:42,480 --> 01:16:44,600
PERSISTENT AND CONSTANT

2313
01:16:44,600 --> 01:16:46,600
INTENSITY INTERVENTION, THE

2314
01:16:46,600 --> 01:16:51,000
PREDICTION IS THAT PEOPLE HAVE A

2315
01:16:51,000 --> 01:16:52,000
RELATIVELY EASY TIME EARLY ON

2316
01:16:52,000 --> 01:16:53,680
CUTTING CALORIES IN THEIR DIET

2317
01:16:53,680 --> 01:16:55,200
BECAUSE THEY HAVEN'T LOST MUCH

2318
01:16:55,200 --> 01:16:56,800
BODY WEIGHT, BUT AS THEY LOSE

2319
01:16:56,800 --> 01:17:00,240
WEIGHT, THE FEEDBACK CONTROL OF

2320
01:17:00,240 --> 01:17:02,280
APPETITE INCREASES TO THE TUNE

2321
01:17:02,280 --> 01:17:03,360
OF 95 KILOCALORIES PER DAY PER

2322
01:17:03,360 --> 01:17:05,080
KILO OF WEIGHT LOSS, AND SO FOR

2323
01:17:05,080 --> 01:17:06,480
THE SAME DEGREE OF EFFORT AND

2324
01:17:06,480 --> 01:17:09,120
THE SAME EXPERIENCE OF HUNGER,

2325
01:17:09,120 --> 01:17:10,680
ENERGY INTAKE WILL GO UP BECAUSE

2326
01:17:10,680 --> 01:17:11,960
IT'S FIGHTING A GREATER AND

2327
01:17:11,960 --> 01:17:14,120
GREATER BATTLE, THE GREATER THE

2328
01:17:14,120 --> 01:17:16,680
INCREASE IN APPETITE BECOMES.

2329
01:17:16,680 --> 01:17:18,160
SO THIS, I HOPE, GIVES PEOPLE A

2330
01:17:18,160 --> 01:17:20,720
PICTURE FOR WHAT FOLKS WITH

2331
01:17:20,720 --> 01:17:22,440
OBESITY EXPERIENCE WHEN YOU JUST

2332
01:17:22,440 --> 01:17:25,080
PRESCRIBE A CALORIE RESTRICTION.

2333
01:17:25,080 --> 01:17:26,880
JUST CUT CALORIES IN YOUR DIET,

2334
01:17:26,880 --> 01:17:28,440
YOU'LL LOSE WEIGHT.

2335
01:17:28,440 --> 01:17:30,920
THE OLD RULE OF THUMB OF THAT

2336
01:17:30,920 --> 01:17:31,640
3500-CALORIES PER POUND DOESN'T

2337
01:17:31,640 --> 01:17:33,920
INCLUDE ANY OF THIS FUNDAMENTAL

2338
01:17:33,920 --> 01:17:35,320
BIOLOGY AND GAVE, I THINK,

2339
01:17:35,320 --> 01:17:36,520
PHYSICIANS THE WRONG IMPRESSION

2340
01:17:36,520 --> 01:17:38,720
FOR MANY, MANY YEARS THAT IT WAS

2341
01:17:38,720 --> 01:17:40,720
A SIMPLE MATTER OF WILLPOWER.

2342
01:17:40,720 --> 01:17:42,200
JUST CUT A LITTLE BIT OF

2343
01:17:42,200 --> 01:17:43,120
CALORIES FROM YOUR DIET AND

2344
01:17:43,120 --> 01:17:44,040
YOU'LL LOSE WEIGHT AND THEN YOU

2345
01:17:44,040 --> 01:17:45,080
CAN GO BACK TO EATING WHAT YOU

2346
01:17:45,080 --> 01:17:46,520
WERE BEFORE AND YOU'LL MAINTAIN

2347
01:17:46,520 --> 01:17:46,960
THE WEIGHT LOSS.

2348
01:17:46,960 --> 01:17:49,720
THAT'S NOT WHAT HAPPENS.

2349
01:17:49,720 --> 01:17:51,840
BUT OF COURSE NOW THAT WE KNOW

2350
01:17:51,840 --> 01:17:54,160
SOMETHING ABOUT THE BIOLOGY THAT

2351
01:17:54,160 --> 01:17:58,040
RESISTS WEIGHT LOSS, THERE'S THE

2352
01:17:58,040 --> 01:17:59,800
HOPE THAT YOU COULD SOMEHOW

2353
01:17:59,800 --> 01:18:00,440
SUBVERT IT.

2354
01:18:00,440 --> 01:18:03,080
AND THERE'S A VARIETY OF PEOPLE

2355
01:18:03,080 --> 01:18:05,280
WHO ARE POPULARIZING VARIOUS

2356
01:18:05,280 --> 01:18:07,400
DIETS THAT COULD POTENTIALLY

2357
01:18:07,400 --> 01:18:08,560
SUBVERT IT, AND ONE OF THE

2358
01:18:08,560 --> 01:18:11,040
POPULAR VERSIONS OF THAT IS

2359
01:18:11,040 --> 01:18:12,640
SOMETHING THAT'S BASED ON A

2360
01:18:12,640 --> 01:18:14,920
MODEL OF OBESITY CALLED THE

2361
01:18:14,920 --> 01:18:16,040
CARBOHYDRATE INSULIN MODEL,

2362
01:18:16,040 --> 01:18:18,760
WHICH IS PROMOTED BY DR. DAVID

2363
01:18:18,760 --> 01:18:19,920
LUDWIG'S GROUP AT HARVARD, WHO

2364
01:18:19,920 --> 01:18:22,360
WROTE A BOOK CALLED "ALWAYS

2365
01:18:22,360 --> 01:18:23,160
HUNGRY" BASED ON THIS IDEA.

2366
01:18:23,160 --> 01:18:24,360
AND HE CORRECTLY POINTS OUT THAT

2367
01:18:24,360 --> 01:18:26,240
WHEN YOU EAT FEWER CALORIES, THE

2368
01:18:26,240 --> 01:18:28,080
BODY BECOMES MORE EFFICIENT AND

2369
01:18:28,080 --> 01:18:30,000
BYRNES FEWER CALORIES, AND AS

2370
01:18:30,000 --> 01:18:32,360
YOUR DESIRE FOR EXTRA CALORIES

2371
01:18:32,360 --> 01:18:33,440
ACTUALLY HEIGHTENS.

2372
01:18:33,440 --> 01:18:35,240
AND THIS COMBINATION OF RISING

2373
01:18:35,240 --> 01:18:36,880
HUNGER AND SLOWING METABOLISM IS

2374
01:18:36,880 --> 01:18:37,640
A RECIPE FOR FAILURE.

2375
01:18:37,640 --> 01:18:38,840
I SHOWED YOU IN THE PREVIOUS

2376
01:18:38,840 --> 01:18:40,480
GRAPH THAT YOU NEED THAT

2377
01:18:40,480 --> 01:18:41,360
LONG-TERM PERSIST AT THE PRESENT

2378
01:18:41,360 --> 01:18:48,120
TIMEPERSISTENT EFFORTDESPITE THR

2379
01:18:48,120 --> 01:18:49,120
WEIGHT LOSS HAS STOPPED IN ORDER

2380
01:18:49,120 --> 01:18:50,320
TO MAINTAIN THAT WEIGHT LOSS.

2381
01:18:50,320 --> 01:18:51,720
HIS IDEA IS THAT MAYBE YOU CAN

2382
01:18:51,720 --> 01:18:52,600
SUBVERT THAT IN SOME WAY.

2383
01:18:52,600 --> 01:18:54,680
SO HE SAYS THAT A MORE EFFECTIVE

2384
01:18:54,680 --> 01:18:56,640
APPROACH IS TO REPROGRAM YOUR

2385
01:18:56,640 --> 01:18:58,240
FAT CELLS TO LOSE WEIGHT BY

2386
01:18:58,240 --> 01:18:59,720
EATING IN A WAY THAT LOWERS

2387
01:18:59,720 --> 01:19:01,120
INSULIN LEVELS AND REDUCES

2388
01:19:01,120 --> 01:19:01,440
INFLAMMATION.

2389
01:19:01,440 --> 01:19:03,000
AND WHEN THIS HAPPENS, FAT CELLS

2390
01:19:03,000 --> 01:19:04,240
CALM DOWN AND RELEASE THEIR

2391
01:19:04,240 --> 01:19:05,840
EXCESS CALORIE STORES AS THE

2392
01:19:05,840 --> 01:19:07,360
BODY BEGINS TO ENJOY BETTER

2393
01:19:07,360 --> 01:19:09,960
ACCESS TO FUEL, METABOLISM RUNS

2394
01:19:09,960 --> 01:19:11,160
BETTER, HUNGER AND CRAVINGS

2395
01:19:11,160 --> 01:19:12,720
SUBSIDE AND WEIGHT LOSS OCCURS

2396
01:19:12,720 --> 01:19:13,160
NATURALLY.

2397
01:19:13,160 --> 01:19:15,680
IT'S A DIET WITHOUT DEPRIVATION.

2398
01:19:15,680 --> 01:19:17,880
SO WHAT IS THE BASIS OF THESE

2399
01:19:17,880 --> 01:19:19,880
PRETTY EXTRAORDINARY CLAIMS?

2400
01:19:19,880 --> 01:19:22,000
WELL, THE IDEA HERE IS THAT AT

2401
01:19:22,000 --> 01:19:23,960
THE LEVEL OF THE FAT CELL, THE

2402
01:19:23,960 --> 01:19:26,320
MAIN THING THAT IS CONTRIBUTING

2403
01:19:26,320 --> 01:19:28,360
TO TRIGLYCERIDE STORAGE IS THE

2404
01:19:28,360 --> 01:19:31,120
AMOUNT OF INSULIN THAT'S

2405
01:19:31,120 --> 01:19:32,360
SURROUNDING THE BODY.

2406
01:19:32,360 --> 01:19:33,880
INDEED INSULIN PLAYS A VERY

2407
01:19:33,880 --> 01:19:36,000
IMPORTANT ROLE AS AARON HAD

2408
01:19:36,000 --> 01:19:39,240
MENTIONED IN RE REGULATING HOW H

2409
01:19:39,240 --> 01:19:40,440
TRIGLYCERIDE IS TAKEN UP FROM

2410
01:19:40,440 --> 01:19:43,280
THE BLOOD AND STORED AS

2411
01:19:43,280 --> 01:19:44,600
TRIGLYCERIDE INSIDE FAT CELLS BY

2412
01:19:44,600 --> 01:19:48,000
THE ENZYME LIPOPROTEIN LIPASE,

2413
01:19:48,000 --> 01:19:51,960
AS WELL AS INHIBITING THE

2414
01:19:51,960 --> 01:19:53,440
HORMONE SENSITIVE LIPASE INSIDE

2415
01:19:53,440 --> 01:19:54,600
FAT CELLS WHICH LIMITS THE

2416
01:19:54,600 --> 01:19:56,920
AMOUNT OF FAT THAT IS RELEASED

2417
01:19:56,920 --> 01:19:57,520
FROM FAT CELLS.

2418
01:19:57,520 --> 01:19:59,840
AND SO THE IDEA OF THIS

2419
01:19:59,840 --> 01:20:01,960
CARBOHYDRATE INSULIN MODEL OF

2420
01:20:01,960 --> 01:20:03,920
OBESITY IS THAT IF YOUR INSULIN

2421
01:20:03,920 --> 01:20:05,360
LEVELS ARE HIGH BECAUSE YOU'RE

2422
01:20:05,360 --> 01:20:07,320
EATING TOO MANY CARBOHYDRATES,

2423
01:20:07,320 --> 01:20:09,120
THEN THAT ESSENTIALLY IS

2424
01:20:09,120 --> 01:20:10,800
TRAPPING YOUR FAT INSIDE YOUR

2425
01:20:10,800 --> 01:20:12,080
FAT CELLS CAUSING THEM TO GO

2426
01:20:12,080 --> 01:20:15,680
INTO THIS ANABOLIC OVERDRIVE

2427
01:20:15,680 --> 01:20:15,960
RESPONSE.

2428
01:20:15,960 --> 01:20:17,240
ACCUMULATING BODY FAT, WHICH

2429
01:20:17,240 --> 01:20:18,720
THEN DEPRIVES THE REST OF THE

2430
01:20:18,720 --> 01:20:21,320
BODY OF CIRCULATING METABOLIC

2431
01:20:21,320 --> 01:20:23,160
FUELS, AND SENSING A PROBLEM OR

2432
01:20:23,160 --> 01:20:25,320
A SORT OF INTERNAL STARVATION

2433
01:20:25,320 --> 01:20:27,920
STATE, YOUR BODY OR YOUR BRAIN

2434
01:20:27,920 --> 01:20:29,840
RECEIVES THE SIGNAL THAT YOU'RE

2435
01:20:29,840 --> 01:20:31,520
STARVING AND THAT INCREASES

2436
01:20:31,520 --> 01:20:32,880
HUNGER, INCREASING ENERGY INTAKE

2437
01:20:32,880 --> 01:20:34,760
AND DECREASING ENERGY

2438
01:20:34,760 --> 01:20:35,040
EXPENDITURE.

2439
01:20:35,040 --> 01:20:36,560
THE WAY THAT DR. LUDWIG

2440
01:20:36,560 --> 01:20:38,120
DESCRIBES IT IN THIS JAMA

2441
01:20:38,120 --> 01:20:40,720
INTERNAL MEDICINE PAPER, HE SAYS

2442
01:20:40,720 --> 01:20:43,000
THAT A HIGH CARBOHYDRATE DIET

2443
01:20:43,000 --> 01:20:47,600
PRODUCES POSTPRANDIAL

2444
01:20:47,600 --> 01:20:48,920
HYPERINULINEMIA PROMOTES

2445
01:20:48,920 --> 01:20:50,120
DEPOSITION OF CALORIES IN FAT

2446
01:20:50,120 --> 01:20:54,080
CELLS INSTEAD OF OXIDATION

2447
01:20:54,080 --> 01:20:55,400
THEREFORE PREDISPOSES TO WEIGHT

2448
01:20:55,400 --> 01:20:56,360
GAIN THROUGH INCREASES IN

2449
01:20:56,360 --> 01:20:58,200
HUNGER, SLOWING METABOLIC RATE

2450
01:20:58,200 --> 01:20:58,800
OR BOTH.

2451
01:20:58,800 --> 01:21:00,280
THIS IS A REALLY INTRIGUING

2452
01:21:00,280 --> 01:21:01,240
MODEL BECAUSE IT MAKES

2453
01:21:01,240 --> 01:21:04,200
PREDICTIONS ABOUT HOW THE BODY

2454
01:21:04,200 --> 01:21:05,840
WEIGHT IS REGULATED AND IT'S

2455
01:21:05,840 --> 01:21:06,520
HAPPENING AT THE LEVEL OF THE

2456
01:21:06,520 --> 01:21:07,960
FAT TISSUE AND NOT AT THE BRAIN,

2457
01:21:07,960 --> 01:21:09,160
AS AARON HAD MENTIONED

2458
01:21:09,160 --> 01:21:11,960
PREVIOUSLY, WHICH IS CURRENTLY

2459
01:21:11,960 --> 01:21:13,880
WHAT MOST OBESITY RESEARCHERS

2460
01:21:13,880 --> 01:21:16,800
THINK IS THE NEXUS OF BODY

2461
01:21:16,800 --> 01:21:19,440
WEIGHT REGULATION.

2462
01:21:19,440 --> 01:21:20,760
SO ONE WAY TO TEST THIS

2463
01:21:20,760 --> 01:21:22,720
HYPOTHESIS WOULD BE TO CHANGE

2464
01:21:22,720 --> 01:21:24,040
THE CARBOHYDRATE AND FAT CONTENT

2465
01:21:24,040 --> 01:21:25,120
OF THE FOOD ENVIRONMENT THAT

2466
01:21:25,120 --> 01:21:27,480
PEOPLE ARE EXPOSED TO, THAT

2467
01:21:27,480 --> 01:21:29,640
SHOULD ALTER INSULIN SECRETION,

2468
01:21:29,640 --> 01:21:31,480
PEOPLE ON A VERY HIGH

2469
01:21:31,480 --> 01:21:32,320
CARBOHYDRATE DIET SHOULD HAVE

2470
01:21:32,320 --> 01:21:33,920
HIGHER INSULIN SECRETION AFTER

2471
01:21:33,920 --> 01:21:35,320
MEALS, THAT SHOULD KEEP THE FAT

2472
01:21:35,320 --> 01:21:36,920
IN THE FAT CELLS AND SHOULD

2473
01:21:36,920 --> 01:21:38,480
CAUSE PEOPLE TO EAT MORE

2474
01:21:38,480 --> 01:21:39,720
CALORIES.

2475
01:21:39,720 --> 01:21:42,760
AND SO ONE OF THE THINGS THAT WE

2476
01:21:42,760 --> 01:21:44,520
DID A COUPLE YEARS AGO, JUST

2477
01:21:44,520 --> 01:21:46,360
BEFORE COVID, WAS THAT WE

2478
01:21:46,360 --> 01:21:47,560
RECRUITED 20 MEN AND WOMEN TO

2479
01:21:47,560 --> 01:21:49,280
THE METABOLIC CLINICAL RESEARCH

2480
01:21:49,280 --> 01:21:51,600
UNIT AT THE NIH CLINICAL CENTER

2481
01:21:51,600 --> 01:21:53,040
THAT AARON DESCRIBED SO NICELY

2482
01:21:53,040 --> 01:21:56,240
AND THEY STAYED WITH US FOR 28

2483
01:21:56,240 --> 01:21:57,560
CONTINUOUS DAYS, 24 HOURS A DAY,

2484
01:21:57,560 --> 01:21:59,440
SEVEN DAYS PER WEEK, AND WE

2485
01:21:59,440 --> 01:22:01,560
RANDOMIZED THEM TO EITHER

2486
01:22:01,560 --> 01:22:04,400
RECEIVE 14 DAYS OF A VERY LOW

2487
01:22:04,400 --> 01:22:06,080
CARB, HIGH FAT DIET, ONE THAT

2488
01:22:06,080 --> 01:22:09,840
WAS DESIGNED TO MINIMIZE INSULIN

2489
01:22:09,840 --> 01:22:10,800
EXCURSIONS, OR A VERY HIGH CASH

2490
01:22:10,800 --> 01:22:18,120
CARBDIET, AND MEASURED THESE FO,

2491
01:22:18,120 --> 01:22:19,360
HOW MANY CALORIES THAT THEY ATE.

2492
01:22:19,360 --> 01:22:21,040
SO WE GAVE THEM MORE THAN ENOUGH

2493
01:22:21,040 --> 01:22:23,080
CALORIES TO EAT TO MAINTAIN

2494
01:22:23,080 --> 01:22:27,840
THEIR WEIGHT, AND GAVE THEM VERY

2495
01:22:27,840 --> 01:22:28,720
SIMPLE INSTRUCTIONS, EAT AS MUCH

2496
01:22:28,720 --> 01:22:29,960
OR AS LITTLE OF THE FOOD YOU'D

2497
01:22:29,960 --> 01:22:30,920
LIKE.

2498
01:22:30,920 --> 01:22:32,240
WE DIDN'T TELL THEM WHAT THE

2499
01:22:32,240 --> 01:22:33,880
PRIMARY OUTCOME OF THE STUDY

2500
01:22:33,880 --> 01:22:34,720
WAS, WE TOLD THEM IT WASN'T A

2501
01:22:34,720 --> 01:22:36,680
WEIGHT LOSS OR WEIGHT GAIN

2502
01:22:36,680 --> 01:22:38,560
STUDY, WE TOLD THEM WE'RE JUST

2503
01:22:38,560 --> 01:22:40,720
INTERESTED HOW THESE DIETS

2504
01:22:40,720 --> 01:22:43,560
AFFECT THEIR BODY AND WE DID A

2505
01:22:43,560 --> 01:22:44,520
NUMBER OF DIFFERENT TESTS AS YOU

2506
01:22:44,520 --> 01:22:46,160
CAN SEE ON THIS GRAPH.

2507
01:22:46,160 --> 01:22:47,720
AFTER 14 DAYS, WE BASICALLY

2508
01:22:47,720 --> 01:22:48,840
SWAPPED THEM TO THE ALTERNATE

2509
01:22:48,840 --> 01:22:50,760
DIET, AGAIN TELLING THEM, EAT

2510
01:22:50,760 --> 01:22:51,840
HOWEVER MUCH OR AS LITTLE AS

2511
01:22:51,840 --> 01:22:52,480
YOU'D LIKE.

2512
01:22:52,480 --> 01:22:55,600
SO HERE'S AN EXAMPLE OF WHAT ONE

2513
01:22:55,600 --> 01:22:57,880
OF THE SEVEN-DAY ROTATING MENUS

2514
01:22:57,880 --> 01:22:59,840
LOOKED LIKE THAT WAS DESIGNED BY

2515
01:22:59,840 --> 01:23:02,000
THE REALLY TALENTED CHEFS AND

2516
01:23:02,000 --> 01:23:03,960
DIETITIANS AT THE NIH CLINICAL

2517
01:23:03,960 --> 01:23:05,480
CENTER NUTRITION DEPARTMENT.

2518
01:23:05,480 --> 01:23:07,280
THIS IS A BREAKFAST ON THE LEFT,

2519
01:23:07,280 --> 01:23:11,720
A LUNCH ON THE -- IN THE MIDDLE

2520
01:23:11,720 --> 01:23:12,440
AND DINNER ON THE RIGHT.

2521
01:23:12,440 --> 01:23:13,920
IT'S A VERY HIGH CARBOHYDRATE

2522
01:23:13,920 --> 01:23:17,640
LOW FAT DIET, AMOUNTED TO ABO

2523
01:23:17,640 --> 01:23:23,520
ABOUT 75% OF TOTAL CALORIES FROM

2524
01:23:23,520 --> 01:23:26,720
CARBS, AND ON THE LOW CARB HIGH

2525
01:23:26,720 --> 01:23:32,560
FAT MEALS, 10% CARB, 75% FAT,

2526
01:23:32,560 --> 01:23:34,120
15% PROTEIN.

2527
01:23:34,120 --> 01:23:40,040
SIM PEAT AS MUCH OR AS LITTLE AS

2528
01:23:40,040 --> 01:23:42,800
THEY'D LIKE ON THESE TWO DIETS.

2529
01:23:42,800 --> 01:23:43,760
POSTPRANDIAL RESPONSES FOR

2530
01:23:43,760 --> 01:23:47,360
INSULIN ON THE HIGH CARB LOW FAT

2531
01:23:47,360 --> 01:23:50,840
DIET WERE MUCH, MUCH HIGHER IN

2532
01:23:50,840 --> 01:23:52,960
THIS MIXED MEAL TEST OF

2533
01:23:52,960 --> 01:23:54,280
ISOCALORIC MEAL TESTS IN THESE

2534
01:23:54,280 --> 01:23:54,920
TWO GROUPS.

2535
01:23:54,920 --> 01:23:55,920
SO WE'RE SETTING UP THE

2536
01:23:55,920 --> 01:23:59,360
SITUATION WHERE THE HIGH CARB

2537
01:23:59,360 --> 01:24:02,520
DIET LEADS TO MUCH HIGHER

2538
01:24:02,520 --> 01:24:03,400
INSULIN LEVELS, KEEP THE FAT

2539
01:24:03,400 --> 01:24:05,200
TRAPPED IN THE FAT CELLS, CAUSE

2540
01:24:05,200 --> 01:24:06,680
THEM TO BE MORE HUNGRY AND EAT

2541
01:24:06,680 --> 01:24:08,680
MORE CALORIES IF THE MODEL IS

2542
01:24:08,680 --> 01:24:09,360
CORRECT.

2543
01:24:09,360 --> 01:24:10,280
UNFORTUNATELY, WE SAW EXACTLY

2544
01:24:10,280 --> 01:24:14,080
THE ON SIT EFFECT.

2545
01:24:14,080 --> 01:24:15,160
 OPPOSITE EFFECT.

2546
01:24:15,160 --> 01:24:16,640
IT WAS THE ONES THAT HAD THE

2547
01:24:16,640 --> 01:24:18,160
MUCH HIGHER INSULIN EXCURSIONS

2548
01:24:18,160 --> 01:24:20,120
THAT LED TO SUBSTANTIALLY LESS

2549
01:24:20,120 --> 01:24:21,440
CALORIE INTAKE IN THESE FOLKS.

2550
01:24:21,440 --> 01:24:23,040
THE SAME FOLKS AS COMPARED TO

2551
01:24:23,040 --> 01:24:27,960
WHEN THEY WERE ON THE LO LOW CAB

2552
01:24:27,960 --> 01:24:29,880
HIGH FAT DIET.

2553
01:24:29,880 --> 01:24:31,640
IN FACT EVERY SINGLE INDIVIDUAL

2554
01:24:31,640 --> 01:24:33,960
OF THESE 20 FOLKS ATE FEWER

2555
01:24:33,960 --> 01:24:36,600
CALORIES ON THE HIGH CARB LOW

2556
01:24:36,600 --> 01:24:38,240
FAT DIET, DESPITE THE MUCH, MUCH

2557
01:24:38,240 --> 01:24:39,840
HIGHER LEVELS OF INSULIN IN THE

2558
01:24:39,840 --> 01:24:41,280
BLOOD.

2559
01:24:41,280 --> 01:24:44,840
THEY DID THIS WITHOUT ANY

2560
01:24:44,840 --> 01:24:45,840
DIFFERENCES IN THEIR APPETITE,

2561
01:24:45,840 --> 01:24:48,160
SO THEY RATED -- THEY BASICALLY

2562
01:24:48,160 --> 01:24:50,000
HAD THE SAME HUNGER SATISFACTION

2563
01:24:50,000 --> 01:24:51,000
FULLNESS AND EATING CAPACITY ON

2564
01:24:51,000 --> 01:24:55,720
BOTH OF THESE DIFFERENT MEALS.

2565
01:24:55,720 --> 01:24:57,320
AND NOT TOO SURPRISING, I GUESS,

2566
01:24:57,320 --> 01:24:59,120
THAT THEY WERE EATING

2567
01:24:59,120 --> 01:25:00,920
700-CALORIES PER DAY LESS ON THE

2568
01:25:00,920 --> 01:25:03,880
HIGH CARB LOW FAT DIET INSTEAD

2569
01:25:03,880 --> 01:25:05,360
OF KEEPING THE FAT TRAPPED IN

2570
01:25:05,360 --> 01:25:07,520
THE FAT CELLS THEIR OVERALL BODY

2571
01:25:07,520 --> 01:25:09,000
FAT MASS LOSS WAS GREATER DURING

2572
01:25:09,000 --> 01:25:11,720
THE HIGH CARB LOW FAT DIET AGAIN

2573
01:25:11,720 --> 01:25:12,880
DESPITE THE HIGHER INSULIN

2574
01:25:12,880 --> 01:25:17,520
LEVELS AS OPPOSED TO THE OTHER

2575
01:25:17,520 --> 01:25:17,720
GROUP.

2576
01:25:17,720 --> 01:25:19,760
I'M GOING TO DIVERT AWAY FROM

2577
01:25:19,760 --> 01:25:21,880
THE DIET WARS IN TERMS OF LOW

2578
01:25:21,880 --> 01:25:23,640
CARB AND LOW FAT DIET.

2579
01:25:23,640 --> 01:25:24,880
THESE WARS HAVE BEEN GOING ON

2580
01:25:24,880 --> 01:25:26,160
FOR DECADES AND DECADES.

2581
01:25:26,160 --> 01:25:27,560
THEY'RE PROBABLY NOT GOING TO

2582
01:25:27,560 --> 01:25:29,000
SUBSIDE ANY TIME SOON, CERTAINLY

2583
01:25:29,000 --> 01:25:30,560
NOT FROM ONE STUDY LIKE I JUST

2584
01:25:30,560 --> 01:25:32,120
SHOWED YOU.

2585
01:25:32,120 --> 01:25:33,520
BUT SOMETHING OCCURRED TO ME

2586
01:25:33,520 --> 01:25:35,120
THAT I THOUGHT WAS KIND OF

2587
01:25:35,120 --> 01:25:35,560
INTERESTING.

2588
01:25:35,560 --> 01:25:38,160
IS THAT BOTH OF THESE DIETS

2589
01:25:38,160 --> 01:25:39,880
TYPICALLY RECOMMEND THAT PEOPLE

2590
01:25:39,880 --> 01:25:43,600
EAT AN ABUNDANCE OF NON-STARCHY

2591
01:25:43,600 --> 01:25:45,880
VEGETABLES, AND THEY TYPICALLY

2592
01:25:45,880 --> 01:25:47,800
ALSO PROVIDE -- THE WRITERS OF

2593
01:25:47,800 --> 01:25:49,160
DIET BOOKS PROVIDE A BUNCH OF

2594
01:25:49,160 --> 01:25:50,760
RECIPES ON HOW TO PREPARE MEALS

2595
01:25:50,760 --> 01:25:53,240
THAT MATCH THE QUALITIES OF

2596
01:25:53,240 --> 01:25:54,760
THEIR PROPOSED DIETS.

2597
01:25:54,760 --> 01:25:57,000
AND AS A RESULT, THEY STEER

2598
01:25:57,000 --> 01:25:59,600
PEOPLE AWAY FROM PREPACKAGED

2599
01:25:59,600 --> 01:26:01,280
FOODS, THE SORT OF READY TO EAT,

2600
01:26:01,280 --> 01:26:02,920
READY TO HEAT MEALS THAT ARE

2601
01:26:02,920 --> 01:26:04,480
OFTEN IN THE FREEZER AISLES OF

2602
01:26:04,480 --> 01:26:05,640
THE SUPERMARKET.

2603
01:26:05,640 --> 01:26:07,040
AND SO IT OCCURRED TO ME THAT,

2604
01:26:07,040 --> 01:26:08,640
YOU KNOW, MAYBE ONE OF THE

2605
01:26:08,640 --> 01:26:09,800
THINGS THAT THEY HAVE IN COMMON

2606
01:26:09,800 --> 01:26:10,880
THAT CAN IMPROVE PEOPLE'S HEALTH

2607
01:26:10,880 --> 01:26:12,920
IS THAT THEY STEER PEOPLE AWAY

2608
01:26:12,920 --> 01:26:17,160
FROM VERY HIGHLY PROCESSED FOODS

2609
01:26:17,160 --> 01:26:21,240
AND TOWARDS PREPARING THEIR OWN

2610
01:26:21,240 --> 01:26:24,520
MEALS FROM WHOLE FOODS AND

2611
01:26:24,520 --> 01:26:25,000
CULINARY INGREDIENTS.

2612
01:26:25,000 --> 01:26:27,160
AND THIS SORT OF ALIGNED WITH

2613
01:26:27,160 --> 01:26:29,080
WHAT'S A RELATIVELY RECENT WAY

2614
01:26:29,080 --> 01:26:30,840
OF LOOKING AT FOODS THAT IS NOT

2615
01:26:30,840 --> 01:26:32,160
FOCUSED ON THE NUTRIENTS, PER

2616
01:26:32,160 --> 01:26:34,400
SE, BUT INSTEAD THE EXTENT AND

2617
01:26:34,400 --> 01:26:36,880
PURPOSE OF PROCESSING.

2618
01:26:36,880 --> 01:26:40,120
AND SO A GROUP IN BRAZIL HAS

2619
01:26:40,120 --> 01:26:41,160
PROPOSED THAT WE START

2620
01:26:41,160 --> 01:26:42,560
CLASSIFYING FOODS NOT BASED ON

2621
01:26:42,560 --> 01:26:44,160
THEIR NUTRIENTS BUT THE EXTENT

2622
01:26:44,160 --> 01:26:46,360
AND PURPOSE OF PROCESSING AND

2623
01:26:46,360 --> 01:26:47,880
DEVELOPING SOMETHING CALLED THE

2624
01:26:47,880 --> 01:26:49,280
NOVA CATEGORIZATION SYSTEM,

2625
01:26:49,280 --> 01:26:51,800
WHERE HE CLASSIFIES FOODS INTO

2626
01:26:51,800 --> 01:26:53,680
THESE FOUR DIFFERENT CATEGORIES.

2627
01:26:53,680 --> 01:26:55,320
UNPROCESSED OR MINIMALLY

2628
01:26:55,320 --> 01:26:57,000
PROCESSED FOODS, PROCESSED

2629
01:26:57,000 --> 01:26:58,640
CULINARY INGREDIENTS, AND

2630
01:26:58,640 --> 01:26:59,720
PROCESSED FOODS WHICH ARE

2631
01:26:59,720 --> 01:27:01,080
ESSENTIALLY COMBINATIONINGS OF

2632
01:27:01,080 --> 01:27:02,880
GROUP 1 AND GROUP 2 FOODS AND

2633
01:27:02,880 --> 01:27:05,560
THEN FINALLY, THIS FOURTH

2634
01:27:05,560 --> 01:27:07,680
CATEGORY, WHICH IS THE BAD GUY,

2635
01:27:07,680 --> 01:27:09,920
THE ULTRAPROCESSED FOODS WHICH

2636
01:27:09,920 --> 01:27:12,000
ARE DEFINED AS FORMULATIONS OF

2637
01:27:12,000 --> 01:27:13,520
SEVERAL INGREDIENTS THAT INCLUDE

2638
01:27:13,520 --> 01:27:15,320
ORIGINAL OR CHEMICALLY MODIFIED

2639
01:27:15,320 --> 01:27:16,960
FOOD SUBSTANCES OBTAINED WITH

2640
01:27:16,960 --> 01:27:18,480
THE FRACTIONING OF WHOLE FOODS

2641
01:27:18,480 --> 01:27:21,120
AND ADDITIVES USED TO MAKE THE

2642
01:27:21,120 --> 01:27:24,160
FINAL PRODUCT PALATABLE OR

2643
01:27:24,160 --> 01:27:25,440
HYPERPALATABLE, AND THE AIM IS

2644
01:27:25,440 --> 01:27:27,280
TO MAKE CONVENIENT TASTE FULL

2645
01:27:27,280 --> 01:27:29,240
AND LOW COST PRODUCTS LIABLE TO

2646
01:27:29,240 --> 01:27:30,400
REPLACE ALL OTHER NOVA FOOD

2647
01:27:30,400 --> 01:27:30,960
GROUPS.

2648
01:27:30,960 --> 01:27:33,120
WHEN I FIRST HEARD ABOUT THIS

2649
01:27:33,120 --> 01:27:35,800
CATEGORIZATION THAT IGNORES

2650
01:27:35,800 --> 01:27:36,880
NUTRIENTS AND DOESN'T TALK MUCH

2651
01:27:36,880 --> 01:27:40,160
ABOUT CALORIES, I WAS VERY

2652
01:27:40,160 --> 01:27:40,440
SKEPTICAL.

2653
01:27:40,440 --> 01:27:42,080
THE FOLKS WHO INTRODUCED ME TO

2654
01:27:42,080 --> 01:27:44,200
THIS IDEA SHOWED ME DOZENS OF

2655
01:27:44,200 --> 01:27:45,760
EPIDEMIOLOGICAL STUDIES LINKING

2656
01:27:45,760 --> 01:27:48,560
ULTRAPROCESSED FOOD INTAKE TO

2657
01:27:48,560 --> 01:27:50,480
OBESITY, AND ONE OF THE THINGS I

2658
01:27:50,480 --> 01:27:52,120
ASKED THEM IS WELL WHAT ARE THE

2659
01:27:52,120 --> 01:27:53,080
POTENTIAL MECHANISMS?

2660
01:27:53,080 --> 01:27:54,240
WHAT THEY CAME BACK TO ME WITH

2661
01:27:54,240 --> 01:27:55,760
WAS BASICALLY A LIST OF

2662
01:27:55,760 --> 01:27:56,000
NUTRIENTS.

2663
01:27:56,000 --> 01:27:58,240
THEY SAID, WELL, ULTRAPROCESSED

2664
01:27:58,240 --> 01:27:59,560
FOODS TEND TO BE HIGH IN SALT,

2665
01:27:59,560 --> 01:28:01,120
SUGAR AND FAT AND LOW IN FIBER

2666
01:28:01,120 --> 01:28:03,240
AND THAT PROMOTES OVEREATING.

2667
01:28:03,240 --> 01:28:05,040
AND I SAID WELL, YOU KNOW,

2668
01:28:05,040 --> 01:28:07,200
THAT'S INTERESTING, BUT YOU JUST

2669
01:28:07,200 --> 01:28:09,640
LISTED A BUNCH OF NUTRIENTS AND

2670
01:28:09,640 --> 01:28:11,840
YOU JUST -- AND YET, YOU KNOW,

2671
01:28:11,840 --> 01:28:13,080
THIS NOVA CATEGORIZATION SYSTEM

2672
01:28:13,080 --> 01:28:14,720
IS NOT REALLY ABOUT THE

2673
01:28:14,720 --> 01:28:15,480
NUTRIENTS.

2674
01:28:15,480 --> 01:28:17,760
SO COULD WE DESIGN A STUDY THAT

2675
01:28:17,760 --> 01:28:19,120
ACTUALLY MATCHED FOR THESE KNEW

2676
01:28:19,120 --> 01:28:22,600
TREENDZ OF CONCERN BUT VARIED IN

2677
01:28:22,600 --> 01:28:23,600
THE DEGREE OF INDUSTRIAL

2678
01:28:23,600 --> 01:28:24,040
PROCESSING?

2679
01:28:24,040 --> 01:28:28,480
AND SO WE DESIGNED ANOTHER STUDY

2680
01:28:28,480 --> 01:28:29,680
VERY SIMILAR TO THE DESIGN OF

2681
01:28:29,680 --> 01:28:31,520
THE LAST STUDY I SHOWED YOU

2682
01:28:31,520 --> 01:28:32,840
WHERE AGAIN PEOPLE SPENT FOUR

2683
01:28:32,840 --> 01:28:34,400
WEEKS CONTINUOUSLY ON OUR

2684
01:28:34,400 --> 01:28:36,040
METABOLIC WARD, 24 HOURS A DAY,

2685
01:28:36,040 --> 01:28:38,040
7 DAYS A WEEK, AND AGAIN, WE

2686
01:28:38,040 --> 01:28:39,840
TOOK OVER THEIR FOOD ENVIRONMENT

2687
01:28:39,840 --> 01:28:41,440
AND GAVE THEM VERY SIMPLE

2688
01:28:41,440 --> 01:28:42,680
INSTRUCTIONS TO EAT AS MUCH OR

2689
01:28:42,680 --> 01:28:45,840
AS LITTLE OF THE FOOD AS WAS

2690
01:28:45,840 --> 01:28:47,480
DESIRED, AND IN THIS CASE, WE

2691
01:28:47,480 --> 01:28:49,760
RANDOMIZED THEM TO EITHER A

2692
01:28:49,760 --> 01:28:51,440
ULTRAPROCESSED DIET OR AN

2693
01:28:51,440 --> 01:28:53,920
UNPROCESSED DIET FOR TWO WEEKS

2694
01:28:53,920 --> 01:28:55,480
AND THEN THEY SWAPPED TO THE

2695
01:28:55,480 --> 01:28:56,360
ALTERNATE DIET.

2696
01:28:56,360 --> 01:28:58,480
AND AGAIN, WE BA BASICALLY TOLD

2697
01:28:58,480 --> 01:29:00,000
THEM WE'RE INTERESTED IN HOW

2698
01:29:00,000 --> 01:29:02,800
THESE DIETS AFFECT YOUR HEALTH,

2699
01:29:02,800 --> 01:29:05,400
EAT AS MUCH OR AS LITTLE AS

2700
01:29:05,400 --> 01:29:06,560
YOU'D LIKE, IT'S NOT A WEIGHT

2701
01:29:06,560 --> 01:29:07,640
LOSS OR WEIGHT GAIN STUDY.

2702
01:29:07,640 --> 01:29:08,560
HERE'S WHAT THE MEALS LOOKED

2703
01:29:08,560 --> 01:29:09,840
LIKE.

2704
01:29:09,840 --> 01:29:10,680
SO HERE'S ONE OF THE SEVEN DAYS

2705
01:29:10,680 --> 01:29:14,200
OF THE ULTRAPROCESSED MEALS, AND

2706
01:29:14,200 --> 01:29:18,000
CRITICALLY OUR TALENTED

2707
01:29:18,000 --> 01:29:19,680
DIETITIANS MATCHED THE OVERALL

2708
01:29:19,680 --> 01:29:21,600
MENUS FOR THE PRESENTED CALORIE,

2709
01:29:21,600 --> 01:29:26,600
THE FAT, THE CARBS, SODIUM,

2710
01:29:26,600 --> 01:29:27,560
FIBER, GLYCEMIC LOAD AND IN THIS

2711
01:29:27,560 --> 01:29:29,840
CASE OF THE ULTRATRA PROCESSED

2712
01:29:29,840 --> 01:29:32,200
MEALS, 80% OF THE CALORIES CAME

2713
01:29:32,200 --> 01:29:33,840
FROM THE CATEGORY FOR

2714
01:29:33,840 --> 01:29:34,520
ULTRAPROCESSED FOOD GROUP.

2715
01:29:34,520 --> 01:29:36,560
IN THE UNPROCESSED GROUP, AGAIN,

2716
01:29:36,560 --> 01:29:40,480
MATCHED FOR THOSE NUTRIENTS AND

2717
01:29:40,480 --> 01:29:41,880
PROPERTIES, 80% OF CALORIES CAME

2718
01:29:41,880 --> 01:29:47,720
FROM THE KA CATEGORY 1 GROUP AN%

2719
01:29:47,720 --> 01:29:49,760
CAME FROM ULTRAPROCESSED FOODS.

2720
01:29:49,760 --> 01:29:51,280
BECAUSE THEY WERE MATCHED FOR

2721
01:29:51,280 --> 01:29:53,200
NUTRIENTS OF CONCERN, MY

2722
01:29:53,200 --> 01:29:54,600
HYPOTHESIS WAS THAT WE WOULDN'T

2723
01:29:54,600 --> 01:29:55,600
SEE MUCH DIFFERENCE IN CALORIE

2724
01:29:55,600 --> 01:29:56,600
INTAKE.

2725
01:29:56,600 --> 01:29:57,720
AND SO THESE FOLKS DID WHAT THEY

2726
01:29:57,720 --> 01:30:00,840
WERE ASKED, THEY AGAIN ATE THE

2727
01:30:00,840 --> 01:30:02,680
SAME DEGREE OF HUNGER, FULLNESS,

2728
01:30:02,680 --> 01:30:04,120
SATISFACTION OR EATING CAPACITY

2729
01:30:04,120 --> 01:30:05,560
ON THESE TWO DIFFERENT DIETS.

2730
01:30:05,560 --> 01:30:08,080
BUT IN THE CASE OF THE

2731
01:30:08,080 --> 01:30:09,200
ULTRAPROCESSED FOOD, CONTRARY TO

2732
01:30:09,200 --> 01:30:11,240
MY EXPECTATIONS, THEY ENDED UP

2733
01:30:11,240 --> 01:30:13,600
EATING ABOUT 500-CALORIES PER

2734
01:30:13,600 --> 01:30:16,240
DAY MORE THAN THE SAME FOLKS

2735
01:30:16,240 --> 01:30:18,080
DURING THE UNPROCESSED DIET.

2736
01:30:18,080 --> 01:30:22,280
AND THAT LED TO BODY FAT GAIN

2737
01:30:22,280 --> 01:30:23,600
SPONTANEOUSLY IN THE

2738
01:30:23,600 --> 01:30:24,880
ULTRAPROCESSED DIET VERSUS BODY

2739
01:30:24,880 --> 01:30:27,120
FAT LOSS IN THE UNPROCESSED DIET

2740
01:30:27,120 --> 01:30:32,560
IN THESE VERY SAME PEOPLE THAT

2741
01:30:32,560 --> 01:30:33,400
SPENT, AGAIN, 28 CONTINUOUS DAYS

2742
01:30:33,400 --> 01:30:38,920
ON OUR METABOLIC UNIT.

2743
01:30:38,920 --> 01:30:41,120
SO WHAT DOES THIS MEAN IN TERMS

2744
01:30:41,120 --> 01:30:43,800
OF THE FEEDBACK AND WHERE WE

2745
01:30:43,800 --> 01:30:45,360
SETTLE IN TERMS OF OUR ENERGY

2746
01:30:45,360 --> 01:30:46,360
EXPENDITURE?

2747
01:30:46,360 --> 01:30:49,320
ONE POSSIBILITY IS THAT OUR FOOD

2748
01:30:49,320 --> 01:30:52,640
ENVIRONMENT SEEMS TO AFFECT THE

2749
01:30:52,640 --> 01:30:53,880
LOCATION OF THIS CURVE.

2750
01:30:53,880 --> 01:30:57,680
IN OTHER WORDS, AN

2751
01:30:57,680 --> 01:30:58,320
ULTRAPROCESSED FOOD ENVIRONMENT

2752
01:30:58,320 --> 01:30:59,880
SHIFTS THE CURVE UPWARDS, PEOPLE

2753
01:30:59,880 --> 01:31:01,440
NOT TRYING TO CHANGE THEIR

2754
01:31:01,440 --> 01:31:02,840
WEIGHT SPONTANEOUSLY EAT MANY,

2755
01:31:02,840 --> 01:31:03,720
MANY MORE CALORIES AND THAT WILL

2756
01:31:03,720 --> 01:31:05,040
GIVE RISE OVER TIME TO WEIGHT

2757
01:31:05,040 --> 01:31:08,760
GAIN AND REEQUILIBRATION AT A

2758
01:31:08,760 --> 01:31:10,520
MUCH HIGHER ENERGY INTAKE AND A

2759
01:31:10,520 --> 01:31:11,760
MUCH HIGHER ENERGY EXPENDITURE

2760
01:31:11,760 --> 01:31:13,360
AND A MUCH HIGHER BODY WEIGHT.

2761
01:31:13,360 --> 01:31:16,320
AND SO MAYBE THIS IS WHAT'S

2762
01:31:16,320 --> 01:31:19,240
UNDERLYING THIS INCREASE IN

2763
01:31:19,240 --> 01:31:20,360
ADULT BODY WEIGHT THAT IS

2764
01:31:20,360 --> 01:31:22,240
CHARACTERISTIC OF OBESITY

2765
01:31:22,240 --> 01:31:23,800
EPIDEMIC THAT THE U.S. IS

2766
01:31:23,800 --> 01:31:25,160
EXPERIENCED OVER THE PAST 50

2767
01:31:25,160 --> 01:31:26,840
YEARS.

2768
01:31:26,840 --> 01:31:28,200
INDEED THE KIND OF QUALITY OF

2769
01:31:28,200 --> 01:31:30,520
THE DIET IN AMERICA HAS CHANGED

2770
01:31:30,520 --> 01:31:32,720
QUITE SUBSTANTIALLY SUCH THAT

2771
01:31:32,720 --> 01:31:34,200
NOW THE DIET IS COMPRISED OF

2772
01:31:34,200 --> 01:31:37,600
MORE THAN 50% OF CALORIES COMING

2773
01:31:37,600 --> 01:31:39,320
FROM ULTRAPROCESSED FOOD AND A

2774
01:31:39,320 --> 01:31:43,160
DECLINE IN THE NUMBER OF

2775
01:31:43,160 --> 01:31:45,200
CALORIES THAT ARE CONSUMED FROM

2776
01:31:45,200 --> 01:31:47,680
ULTRAPROCESSED FOODS OR CULINARY

2777
01:31:47,680 --> 01:31:48,560
INGREDIENTS INDICATING THAT MORE

2778
01:31:48,560 --> 01:31:50,240
PEOPLE ARE EATING PREPREPARED

2779
01:31:50,240 --> 01:31:51,400
MEALS EITHER AT HOME OR AWAY

2780
01:31:51,400 --> 01:31:51,800
FROM HOME.

2781
01:31:51,800 --> 01:31:52,840
IN FACT, ONE OF THE THINGS

2782
01:31:52,840 --> 01:31:54,480
THAT'S VERY INTERESTING ALSO IS

2783
01:31:54,480 --> 01:31:58,000
THAT THE AMOUNT OF CALORIE

2784
01:31:58,000 --> 01:32:01,120
INTAKE REQUIRED TO EXPLAIN THE

2785
01:32:01,120 --> 01:32:03,400
INCREASE IN BODY WEIGHT THAT'S

2786
01:32:03,400 --> 01:32:05,760
OBSERVED IN AMERICA OVER THE

2787
01:32:05,760 --> 01:32:07,400
PAST 50 YEARS IS MUCH, MUCH LESS

2788
01:32:07,400 --> 01:32:09,080
THAN THE INCREASE IN CALORIES IN

2789
01:32:09,080 --> 01:32:13,120
THE FOOD SUPPLY, EITHER MEASURED

2790
01:32:13,120 --> 01:32:14,960
BY THE USDA OR THE UNITED

2791
01:32:14,960 --> 01:32:15,800
NATIONS FOOD AND AGRICULTURE

2792
01:32:15,800 --> 01:32:16,480
ORGANIZATION.

2793
01:32:16,480 --> 01:32:17,840
SO I'M PLOTTING HERE THE BLACK

2794
01:32:17,840 --> 01:32:19,760
LINE IS WHAT WOULD BE EXPECTED

2795
01:32:19,760 --> 01:32:22,840
TO MAINTAIN THAT HIGHER ADULT

2796
01:32:22,840 --> 01:32:24,360
BODY WEIGHT THAT AMOUNTS TO

2797
01:32:24,360 --> 01:32:25,840
ABOUT 250-CALORIES PER DAY

2798
01:32:25,840 --> 01:32:27,240
INCREASE SINCE THE 1970s,

2799
01:32:27,240 --> 01:32:28,600
WHEREAS THE ACTUAL NUMBER OF

2800
01:32:28,600 --> 01:32:31,360
CALORIES IN THE FOOD SUPPLY IS

2801
01:32:31,360 --> 01:32:32,880
ESTIMATED BY THESE FOOD BALANCE

2802
01:32:32,880 --> 01:32:35,000
SHEETS HAS INCREASED PER CAPITA

2803
01:32:35,000 --> 01:32:36,920
BY A MUCH, MUCH GREATER EXTENT.

2804
01:32:36,920 --> 01:32:38,440
IN FACT, THAT PREDIBTS THAT

2805
01:32:38,440 --> 01:32:41,160
THERE'S AN INCREASE IN FOOD

2806
01:32:41,160 --> 01:32:43,360
WASTE ON A PER CAPITA BASIS, SO

2807
01:32:43,360 --> 01:32:44,760
THE DIFFERENCE BETWEEN THOSE

2808
01:32:44,760 --> 01:32:46,400
CURVES IS BASICALLY THE BLUE

2809
01:32:46,400 --> 01:32:49,000
LINE HERE, CALCULATED FROM OUR

2810
01:32:49,000 --> 01:32:51,560
MODEL, AND IF WE GO TO THE

2811
01:32:51,560 --> 01:32:52,200
ENVIRONMENTAL PROTECTION AGENCY,

2812
01:32:52,200 --> 01:32:53,960
THEY ACTUALLY KEEP TRACK OF WHAT

2813
01:32:53,960 --> 01:32:56,200
IS DUMPED IN LANDFILLS AND ONE

2814
01:32:56,200 --> 01:32:57,400
OF THE PIECES OF DATA THEY

2815
01:32:57,400 --> 01:32:59,200
PUBLISH IS THE AMOUNT OF SOLID

2816
01:32:59,200 --> 01:33:01,000
FOOD WASTE.

2817
01:33:01,000 --> 01:33:02,640
THEY DON'T PUBLISH THE DATA PER

2818
01:33:02,640 --> 01:33:03,800
CAPITA, BUT WE CALCULATED THEIR

2819
01:33:03,800 --> 01:33:05,160
DATA PER CAPITA AND THERE'S BEEN

2820
01:33:05,160 --> 01:33:08,360
AN EXACTLY PARALLEL 50%

2821
01:33:08,360 --> 01:33:09,240
PROGRESSIVE INCREASE IN FOOD

2822
01:33:09,240 --> 01:33:11,960
WASTE SINCE THE 1970s.

2823
01:33:11,960 --> 01:33:13,480
SO THIS REALLY SUGGESTS

2824
01:33:13,480 --> 01:33:15,280
SOMETHING KIND OF STRIKING WHICH

2825
01:33:15,280 --> 01:33:18,800
IS THAT WE'VE GOTTEN SO GOOD AT

2826
01:33:18,800 --> 01:33:21,840
GROWING THESE STAPLE CROPS OF

2827
01:33:21,840 --> 01:33:24,480
SOY AND WEIGHT AND CORN WITH

2828
01:33:24,480 --> 01:33:26,880
VERY HIGH YIELDS AND HAVE TURNED

2829
01:33:26,880 --> 01:33:29,120
THESE VERY CHEAP COMMODITY

2830
01:33:29,120 --> 01:33:32,760
INGREDIENTS INTO THIS MYRIAD OF

2831
01:33:32,760 --> 01:33:33,480
ULTRAPROCESSED FOOD PRODUCTS

2832
01:33:33,480 --> 01:33:36,480
THAT ARE ENGINEERED TO BE

2833
01:33:36,480 --> 01:33:37,240
PALATABLE AND CONVENIENT AND

2834
01:33:37,240 --> 01:33:39,440
HAVE ALL SORTS OF WONDERFUL

2835
01:33:39,440 --> 01:33:43,360
PROPERTIES, LONG SHELF LIFE AND

2836
01:33:43,360 --> 01:33:43,880
RELATIVELY INEXPENSIVE.

2837
01:33:43,880 --> 01:33:46,400
AND WE HAVE NOW A FOOD SYSTEM

2838
01:33:46,400 --> 01:33:49,000
THAT IS DOMINATED BY THESE

2839
01:33:49,000 --> 01:33:50,840
PRODUCTS IN THE U.S.

2840
01:33:50,840 --> 01:33:53,240
AND SO ONE HYPOTHESIS IS THAT

2841
01:33:53,240 --> 01:33:54,720
THIS INCREASED RELIANCE AND

2842
01:33:54,720 --> 01:33:56,160
INCREASED SHARE OF

2843
01:33:56,160 --> 01:33:57,720
ULTRAPROCESSED FOODS IN THE U.S.

2844
01:33:57,720 --> 01:34:01,200
FOOD SUPPLY AND INDEED AROUND

2845
01:34:01,200 --> 01:34:03,880
THE WORLD IN INCREASING AMOUNTS

2846
01:34:03,880 --> 01:34:04,800
HAS POTENTIALLY INCREASED

2847
01:34:04,800 --> 01:34:05,880
OBESITY.

2848
01:34:05,880 --> 01:34:07,400
AND THAT'S THE RESULT OF YEARS

2849
01:34:07,400 --> 01:34:09,800
OF AGRICULTURAL RESEARCH,

2850
01:34:09,800 --> 01:34:11,880
CHANGES IN FARM TECHNOLOGY AND

2851
01:34:11,880 --> 01:34:14,520
POLICY THAT HAVE ESSENTIALLY U 

2852
01:34:14,520 --> 01:34:16,080
USED CHEAP FOSSIL FUEL AND

2853
01:34:16,080 --> 01:34:18,640
HYBRID SEEDS TO GENERATE A

2854
01:34:18,640 --> 01:34:21,120
MASSIVE INCREASE IN YIELD AND

2855
01:34:21,120 --> 01:34:22,440
PRODUCTION OF THESE GRAIN

2856
01:34:22,440 --> 01:34:25,440
PRODUCTS LIKE CORN AND SOY AND

2857
01:34:25,440 --> 01:34:28,040
WHEAT, FOUND WAYS TO FEED THESE

2858
01:34:28,040 --> 01:34:29,880
GRAINS TO CATTLE AND OTHER

2859
01:34:29,880 --> 01:34:30,640
LIVESTOCK THAT WOULD NOT

2860
01:34:30,640 --> 01:34:32,360
NORMALLY EAT THOSE FOODS AS WELL

2861
01:34:32,360 --> 01:34:34,240
AS CONVERT THOSE GRAINS DIRECTLY

2862
01:34:34,240 --> 01:34:35,400
INTO THESE ULTRAPROCESSED FOODS

2863
01:34:35,400 --> 01:34:37,040
THAT HAVE THESE CHEAP INPUTS

2864
01:34:37,040 --> 01:34:39,680
LEADING TO THE CONVENIENT AND

2865
01:34:39,680 --> 01:34:40,360
INEXPENSIVE ULTRAPROCESSED FOOD

2866
01:34:40,360 --> 01:34:42,280
IN THE FOOD SUPPLY, AND THE

2867
01:34:42,280 --> 01:34:44,880
AMAZING THING TO ME IS THAT TWO

2868
01:34:44,880 --> 01:34:48,080
THIRDS OF THAT INCREASE IN FOODS

2869
01:34:48,080 --> 01:34:50,080
AVAILABLE IN THE FOOD SUPPLY

2870
01:34:50,080 --> 01:34:53,040
WENT IN THE TRASH AND ONLY

2871
01:34:53,040 --> 01:34:53,840
ONE-THIRD WAS ASSOCIATED WITH

2872
01:34:53,840 --> 01:34:55,560
THE INCREASE IN CALORIE INTAKE

2873
01:34:55,560 --> 01:34:57,680
REQUIRED TO EXPLAIN INCREASED

2874
01:34:57,680 --> 01:34:59,720
OBESITY IN THE UNITED STATES.

2875
01:34:59,720 --> 01:35:02,280
SO WITH THAT, I'LL END MY TALK

2876
01:35:02,280 --> 01:35:03,520
AND I LOOK FORWARD TO THE

2877
01:35:03,520 --> 01:35:04,120
QUESTION AND ANSWER SESSION.

2878
01:35:04,120 --> 01:35:13,840
THANK YOU.

2879
01:35:13,840 --> 01:35:14,880
>>THANK YOU VERY MUCH SH
KEVIN.

2880
01:35:14,880 --> 01:35:17,640
THAT IS CERTAINLY AN EXCITING

2881
01:35:17,640 --> 01:35:19,640
AND SOMEWHAT FRIGHTENING

2882
01:35:19,640 --> 01:35:25,080
PROSPECT THAT YOU -- WELL, AS

2883
01:35:25,080 --> 01:35:27,080
ANTICIPATED, WE HAVE LOTS OF

2884
01:35:27,080 --> 01:35:29,280
QUESTIONS.

2885
01:35:29,280 --> 01:35:32,760
SO OUR TIME GOES UNTIL 6:00,

2886
01:35:32,760 --> 01:35:39,840
WHEN THEY SHUT EVERYTHING DOWN.

2887
01:35:39,840 --> 01:35:40,960
SO I'M GOING TO ASK YOU SOME OF

2888
01:35:40,960 --> 01:35:43,120
THESE QUESTIONS AND PERHAPS

2889
01:35:43,120 --> 01:35:44,720
DON'T TRY AND GO TOO FAR I A WAY

2890
01:35:44,720 --> 01:35:55,240
SO WE CAN GET TO MOST OF THEM.

2891
01:35:56,160 --> 01:35:57,240
SO ONE OF THE QUESTIONS THAT IS

2892
01:35:57,240 --> 01:36:00,200
ASKED IS, HOW DOES HIGH BLOOD

2893
01:36:00,200 --> 01:36:04,680
PRESSURE RELATE TO THE FAT BRAIN

2894
01:36:04,680 --> 01:36:05,320
CARDIOENDOCRINE SYSTEM?

2895
01:36:05,320 --> 01:36:07,400
DOES BLOOD PRESSURE ITSELF

2896
01:36:07,400 --> 01:36:10,800
INFLUENCE THE FAT CELL BRAIN

2897
01:36:10,800 --> 01:36:12,760
ENDOCRINE SYSTEM?

2898
01:36:12,760 --> 01:36:15,400
YOUR RESULTS SEEM TO BE

2899
01:36:15,400 --> 01:36:16,400
INDEPENDENT OF BLOOD PRESSURE,

2900
01:36:16,400 --> 01:36:17,680
BUT ONE MIGHT EXPECT THAT BLOOD

2901
01:36:17,680 --> 01:36:20,440
PRESSURE COULD BE A GREAT

2902
01:36:20,440 --> 01:36:22,800
MITIGATING FACTOR, BECAUSE IT

2903
01:36:22,800 --> 01:36:25,080
COULD INFLUENCE THE

2904
01:36:25,080 --> 01:36:27,480
BETA-ADRENERGIC SYSTEM.

2905
01:36:27,480 --> 01:36:29,880
SO WOULD EITHER OF YOU WISH TO

2906
01:36:29,880 --> 01:36:30,760
COMMENT ABOUT THIS?

2907
01:36:30,760 --> 01:36:33,080
PERHAPS, AARON, YOU'D LIKE TO GO

2908
01:36:33,080 --> 01:36:34,280
FIRST.

2909
01:36:34,280 --> 01:36:35,000
>>SURE.

2910
01:36:35,000 --> 01:36:40,520
I THINK IT'S VERY IMPORTANT TO

2911
01:36:40,520 --> 01:36:41,400
CONSIDER HOW BLOOD PRESSURE

2912
01:36:41,400 --> 01:36:44,960
INTERACTS WITH OTHER ASPECTS OF

2913
01:36:44,960 --> 01:36:47,600
THE CARDIOMETABOLIC SYSTEM.

2914
01:36:47,600 --> 01:36:51,120
AND SO THE FIRST QUESTION IS DO

2915
01:36:51,120 --> 01:36:53,040
PEOPLE WHO HAVE HIGHER BLOOD

2916
01:36:53,040 --> 01:36:54,880
PRESSURES, DO THEY HAVE HIGHER

2917
01:36:54,880 --> 01:36:57,240
LEVELS OF BROWN FAT -- ENERGY

2918
01:36:57,240 --> 01:36:58,240
PRESSURE, IT DOESN'T SEEM TO BE

2919
01:36:58,240 --> 01:36:59,320
THE CASE FOR ANY NUMBER OF

2920
01:36:59,320 --> 01:37:00,800
DIFFERENT REASONS.

2921
01:37:00,800 --> 01:37:02,280
AND CERTAINLY WHERE YOU

2922
01:37:02,280 --> 01:37:04,560
INTERVENE IS GOING TO IMPACT

2923
01:37:04,560 --> 01:37:05,560
WHETHER OR NOT THE BLOOD

2924
01:37:05,560 --> 01:37:06,480
PRESSURE IS AFFECTED.

2925
01:37:06,480 --> 01:37:09,240
SO FOR EXAMPLE, IF YOU WANT TO

2926
01:37:09,240 --> 01:37:13,040
DRIVE FAT -- WHITE FAT BREAKD 

2927
01:37:13,040 --> 01:37:14,120
BREAKDOWN, TO BURN EXCESS FAT

2928
01:37:14,120 --> 01:37:17,440
AND YOU WANT TO INCREASE FAT

2929
01:37:17,440 --> 01:37:19,440
METABOLIC ACTIVITY TO REDUCE THE

2930
01:37:19,440 --> 01:37:21,400
AMOUNT THAT'S IN THE BODY, THE

2931
01:37:21,400 --> 01:37:23,760
ADRENERGIC SYSTEM IS THE

2932
01:37:23,760 --> 01:37:25,240
SIMPLEST CONCEPTUAL WAY BECAUSE

2933
01:37:25,240 --> 01:37:26,960
IT'S HARD WIRED INTO OUR SYSTEM,

2934
01:37:26,960 --> 01:37:28,480
SO YOU CAN HAVE AN INCREASE IN

2935
01:37:28,480 --> 01:37:29,400
BLOOD PRESSURE ON THE BACK END,

2936
01:37:29,400 --> 01:37:32,120
AS WE SAW WITH MIRABEGRON AND HE

2937
01:37:32,120 --> 01:37:33,240
IF HE DRIN BEFORE THAT IN YOU A

2938
01:37:33,240 --> 01:37:35,000
OF OUR PUBLICATIONS AND OTHER

2939
01:37:35,000 --> 01:37:37,800
GROUPS AS WELL.

2940
01:37:37,800 --> 01:37:38,680
CAREY, FOR EXAMPLE, IN

2941
01:37:38,680 --> 01:37:39,000
AUSTRALIA.

2942
01:37:39,000 --> 01:37:42,200
SO I THINK IT'S A GREAT POINT

2943
01:37:42,200 --> 01:37:45,200
THAT BLOOD PRESSURE HAS TO BE

2944
01:37:45,200 --> 01:37:48,880
ACCOUNTED FOR AND THERE ARE

2945
01:37:48,880 --> 01:37:50,000
INTERVENTIONS LIKELY TO BE MORE

2946
01:37:50,000 --> 01:37:51,520
SAFE AND NOT INVOLVE INCREASES

2947
01:37:51,520 --> 01:37:52,760
IN BLOOD PRESSURE BUT YOU NEVER

2948
01:37:52,760 --> 01:37:54,160
KNOW WHAT KIND OF COMMON

2949
01:37:54,160 --> 01:37:55,200
REGULATORY RESPONSE WILL COME UP

2950
01:37:55,200 --> 01:37:55,960
AND THEREFORE YOU HAVE TO

2951
01:37:55,960 --> 01:37:57,880
MONITOR IT CAREFULLY.

2952
01:37:57,880 --> 01:38:05,000
>>SO RELATED TO THAT IS
THE

2953
01:38:05,000 --> 01:38:08,800
QUESTION OF WHETHER DISREGULATED

2954
01:38:08,800 --> 01:38:13,080
BROWN FAT ACTIVATION, IS THAT

2955
01:38:13,080 --> 01:38:18,320
ASSOCIATED WITH CHANGES IN HARD

2956
01:38:18,320 --> 01:38:20,720
COLD SENSITIVITY, OR IS IT THE

2957
01:38:20,720 --> 01:38:22,960
HARD COLD SENSITIVITY THAT DRIVE

2958
01:38:22,960 --> 01:38:24,880
THE PROCESS?

2959
01:38:24,880 --> 01:38:26,200
>>THAT'S A BILLION DOLLAR

2960
01:38:26,200 --> 01:38:26,720
QUESTION RIGHT THERE.

2961
01:38:26,720 --> 01:38:29,960
I WOULD SAY THAT THERE WAS A

2962
01:38:29,960 --> 01:38:32,000
VERY NICE WORK, SOME FROM OUR

2963
01:38:32,000 --> 01:38:36,360
COLLEAGUES IN CANADA, SOME WORK

2964
01:38:36,360 --> 01:38:37,880
THAT I KNOW MORE DIRECTLY FROM

2965
01:38:37,880 --> 01:38:42,280
OUR GROUP AT NIH LED BY KONG

2966
01:38:42,280 --> 01:38:44,600
CHEN AND -- AS THE FIRST AUTHOR

2967
01:38:44,600 --> 01:38:47,280
WHERE THEY LOOKED AT BROWN FAT

2968
01:38:47,280 --> 01:38:49,000
ACTIVITY AND COLD TOLERANCE IN A

2969
01:38:49,000 --> 01:38:50,440
GROUP OF MEN WITH OBESITY AND

2970
01:38:50,440 --> 01:38:53,720
THEN A GROUP OF MEN WHO ARE LE 

2971
01:38:53,720 --> 01:38:54,560
LEAN.

2972
01:38:54,560 --> 01:38:55,920
AND THE MEAN RESULT OF THAT

2973
01:38:55,920 --> 01:38:59,760
STUDY WAS TO FIND THAT MEN WITH

2974
01:38:59,760 --> 01:39:03,080
OBESITY HAD LESS COLD TOLERANCE

2975
01:39:03,080 --> 01:39:05,400
AND LESS ABILITY TO GENERATE

2976
01:39:05,400 --> 01:39:09,320
HEAT THAN MEN WHO WERE LEAN, AND

2977
01:39:09,320 --> 01:39:13,040
PART OF THAT DIFFERENCE BETWEEN

2978
01:39:13,040 --> 01:39:14,080
THE MEN WITH LEANNESS AND THE

2979
01:39:14,080 --> 01:39:16,080
MEN WITH OBESITY IS THAT THE MEN

2980
01:39:16,080 --> 01:39:17,800
WITH OBESITY HAD LESS FUNCTIONAL

2981
01:39:17,800 --> 01:39:18,440
BROWN FAT.

2982
01:39:18,440 --> 01:39:20,040
IT WASN'T SO SIMPLE TO FORM A

2983
01:39:20,040 --> 01:39:20,640
DIRECT CORRELATION BETWEEN THE

2984
01:39:20,640 --> 01:39:22,920
TWO, BUT IT CERTAINLY DOES

2985
01:39:22,920 --> 01:39:25,920
APPEAR THAT PEOPLE WHO HAVE

2986
01:39:25,920 --> 01:39:27,720
DISREGULATED THAT ARE ASSOCIATED

2987
01:39:27,720 --> 01:39:31,880
WITH DEFICIENCIES IN COLD

2988
01:39:31,880 --> 01:39:32,160
RESPONSES.

2989
01:39:32,160 --> 01:39:34,600
HEAT, WE DIDN'T STUDY.

2990
01:39:34,600 --> 01:39:35,480
THAT IS A CLINICAL TRIAL THAT

2991
01:39:35,480 --> 01:39:37,880
SHOULD BE GOING ON SOON, BUT WE

2992
01:39:37,880 --> 01:39:38,560
DON'T KNOW THAT OTHER SIDE OF

2993
01:39:38,560 --> 01:39:40,240
IT, JUST COLD.

2994
01:39:40,240 --> 01:39:43,440
>>SO KEVIN, AS A QUESTION
OF

2995
01:39:43,440 --> 01:39:45,840
WHETHER YOU THINK THE DRASTIC

2996
01:39:45,840 --> 01:39:47,600
DROP IN THE RESTING METABOLIC

2997
01:39:47,600 --> 01:39:53,000
RATE IN YOUR STUDY WHICH WAS

2998
01:39:53,000 --> 01:39:56,880
BROUGHT ON BY RAPID WEIGHT LOSS,

2999
01:39:56,880 --> 01:39:59,360
IS THAT SORT OF ANALOGOUS TO THE

3000
01:39:59,360 --> 01:40:02,760
BODY GOING INTO A KIND OF PANIC

3001
01:40:02,760 --> 01:40:06,320
MODE, SORT OF MAXIMIZING

3002
01:40:06,320 --> 01:40:12,320
CONSERVATION AND IF SO, IS THAT

3003
01:40:12,320 --> 01:40:15,240
LINKED TO THE ADRENERGIC NERVOUS

3004
01:40:15,240 --> 01:40:15,760
SYSTEM?

3005
01:40:15,760 --> 01:40:16,280
>>YEAH, GREAT QUESTION.

3006
01:40:16,280 --> 01:40:17,840
SO I THINK THERE'S KIND OF TWO

3007
01:40:17,840 --> 01:40:19,560
PHASES OF THIS, WHICH ARE

3008
01:40:19,560 --> 01:40:20,520
IMPORTANT TO KIND OF

3009
01:40:20,520 --> 01:40:21,400
DISTINGUISH.

3010
01:40:21,400 --> 01:40:23,760
ONE IS THE SORT OF ACTIVE WEIGHT

3011
01:40:23,760 --> 01:40:25,080
LOSS PHASE WHERE PEOPLE HAVE

3012
01:40:25,080 --> 01:40:27,120
DRASTICALLY CUT CALORIES AND ARE

3013
01:40:27,120 --> 01:40:30,320
CONTINUING TO LOSE WEIGHT, AND

3014
01:40:30,320 --> 01:40:34,680
IT SEEMS LIKE THAT RESPONSE THAT

3015
01:40:34,680 --> 01:40:36,080
DROP IN RESTING METABOLIC RATE

3016
01:40:36,080 --> 01:40:37,080
IS PROPORTIONAL TO HOW MUCH

3017
01:40:37,080 --> 01:40:38,800
PEOPLE HAVE CUT THEIR CALORIES

3018
01:40:38,800 --> 01:40:41,320
IN THEIR DIET.

3019
01:40:41,320 --> 01:40:44,040
AND IT SEEMS TO BE RELATED TO

3020
01:40:44,040 --> 01:40:45,400
SYMPATHETIC NERVOUS SYSTEM TONE,

3021
01:40:45,400 --> 01:40:47,640
IT SEEMS TO BE RELATED TO THE

3022
01:40:47,640 --> 01:40:49,680
DROP IN LEPTIN, IT MIGHT BE

3023
01:40:49,680 --> 01:40:51,840
RELATED TO THE THYROID ACCESS,

3024
01:40:51,840 --> 01:40:53,240
BUT THEN THERE'S THIS LONGER

3025
01:40:53,240 --> 01:40:55,160
TERM EFFECT WHICH WE OBSERVE

3026
01:40:55,160 --> 01:40:56,880
WHERE PEOPLE ARE NO LONGER

3027
01:40:56,880 --> 01:40:57,520
ACTIVELY LOSING WEIGHT, SO AT

3028
01:40:57,520 --> 01:40:59,320
SIX YEARS, THERE SEEMS TO BE

3029
01:40:59,320 --> 01:41:02,120
THIS CONTINUED SUPPRESSION OF

3030
01:41:02,120 --> 01:41:03,080
RESTING METABOLIC RATE.

3031
01:41:03,080 --> 01:41:05,320
DESPITE THE FACT THAT THEY'RE NO

3032
01:41:05,320 --> 01:41:07,000
NO LONGER IN THIS NEGATIVE

3033
01:41:07,000 --> 01:41:07,760
ENERGY BALANCE STATE.

3034
01:41:07,760 --> 01:41:09,600
AND THE QUESTION IS, IS THERE

3035
01:41:09,600 --> 01:41:10,800
SOMETHING DIFFERENT GOING ON

3036
01:41:10,800 --> 01:41:12,000
THERE.

3037
01:41:12,000 --> 01:41:13,960
AND I THINK THAT THERE'S SOME

3038
01:41:13,960 --> 01:41:15,400
INTRIGUING DATA FROM OTHER

3039
01:41:15,400 --> 01:41:16,760
PEOPLE'S STUDIES THAT SUGGEST

3040
01:41:16,760 --> 01:41:20,400
THAT IT'S POSSIBLE THAT ONE OF

3041
01:41:20,400 --> 01:41:21,760
THE THINGS THAT'S INTERESTING IS

3042
01:41:21,760 --> 01:41:25,080
THAT OUR PARTICIPANTS HAD BECOME

3043
01:41:25,080 --> 01:41:25,680
VERY PHYSICALLY ACTIVE ON

3044
01:41:25,680 --> 01:41:26,040
AVERAGE.

3045
01:41:26,040 --> 01:41:27,640
THERE WAS QUITE A BIT OF

3046
01:41:27,640 --> 01:41:29,120
VARIABILITY, BUT THE FOLKS WHO

3047
01:41:29,120 --> 01:41:31,080
HAD BECOME THE MOST PHYSICALLY

3048
01:41:31,080 --> 01:41:32,760
ACTIVE INDEED WERE THE ONES WHO

3049
01:41:32,760 --> 01:41:37,000
HAD THE GLAI THE GREATEST SUSTAD

3050
01:41:37,000 --> 01:41:38,160
REDUCTION IN THE RESTING

3051
01:41:38,160 --> 01:41:40,520
METABOLIC RATE OVER THE SIX YEAR

3052
01:41:40,520 --> 01:41:40,960
TIME PERIOD.

3053
01:41:40,960 --> 01:41:42,840
SO THERE'S AN INTRIGUING IDEA

3054
01:41:42,840 --> 01:41:44,520
THAT AS CHRONIC PHYSICAL

3055
01:41:44,520 --> 01:41:49,040
ACTIVITY INCREASES, PERHAPS THE

3056
01:41:49,040 --> 01:41:50,360
BODY IS LEARNING TO EXPEND LESS

3057
01:41:50,360 --> 01:41:54,080
ON OTHER ASPECTS OF MAYBE IMMUNE

3058
01:41:54,080 --> 01:41:55,440
SYSTEM FUNCTION IS GOING DOWN

3059
01:41:55,440 --> 01:41:56,880
BECAUSE INFLAMMATION IS

3060
01:41:56,880 --> 01:41:58,040
DECREASED BECAUSE OF THE

3061
01:41:58,040 --> 01:41:59,640
INCREASED PHYSICAL ACTIVITY,

3062
01:41:59,640 --> 01:42:01,240
MAYBE LESS ENERGY IS SPENT ON

3063
01:42:01,240 --> 01:42:03,080
OTHER PHYSIOLOGICAL FUNCTIONS.

3064
01:42:03,080 --> 01:42:04,880
UNFORTUNATELY WE JUST DON'T KNOW

3065
01:42:04,880 --> 01:42:07,080
HOW TO TIE EVERY CALORIE THAT WE

3066
01:42:07,080 --> 01:42:10,280
CAN MEASURE IN OUR INSTRUMENTS

3067
01:42:10,280 --> 01:42:12,000
TO EXACT BIOLOGICAL FUNCTIONS OF

3068
01:42:12,000 --> 01:42:13,320
DIFFERENT ORGANS AND DIFFERENT

3069
01:42:13,320 --> 01:42:14,120
CELL TYPES OF THE BODY.

3070
01:42:14,120 --> 01:42:15,280
THAT WOULD BE THE DREAM, RIGHT,

3071
01:42:15,280 --> 01:42:16,600
TO BE ABLE TO JUST COUNT UP ALL

3072
01:42:16,600 --> 01:42:18,480
THE FUNCTIONS OF ALL THE

3073
01:42:18,480 --> 01:42:19,840
DIFFERENT CELLS AND BE ABLE TO

3074
01:42:19,840 --> 01:42:22,160
ASSIGN AN ATP COST AND JUST SAY

3075
01:42:22,160 --> 01:42:23,760
OH, YES, WE CAN EXPLAIN EVERY

3076
01:42:23,760 --> 01:42:25,640
CALORIE THAT'S EXPENDED, BUT IT

3077
01:42:25,640 --> 01:42:29,240
IS AN INTERESTING OBSERVATION

3078
01:42:29,240 --> 01:42:31,600
THAT, FOR EXAMPLE, PEOPLE IN

3079
01:42:31,600 --> 01:42:32,200
HUNTER GATHERER TRIBES WHO ARE

3080
01:42:32,200 --> 01:42:33,560
VERY, VERY ACTIVE, THIS IS WORK

3081
01:42:33,560 --> 01:42:37,560
PRIMARILY FROM HER MAN PONZER'S

3082
01:42:37,560 --> 01:42:39,200
GROUP, BURN VERY, VERY SIMILAR

3083
01:42:39,200 --> 01:42:40,720
NUMBERS OF TOTAL CALORIES AS

3084
01:42:40,720 --> 01:42:42,160
SEDENTARY FOLKS WHO ARE MUCH

3085
01:42:42,160 --> 01:42:43,360
HEAVIER BUT THEN IF YOU ADJUST

3086
01:42:43,360 --> 01:42:47,200
FOR YOUR BODY COMPOSITION CHA 

3087
01:42:47,200 --> 01:42:49,760
CHANGE, THEY END UP BURNING A

3088
01:42:49,760 --> 01:42:50,520
MYSTERIOUSLY SIMILAR AMOUNT OF

3089
01:42:50,520 --> 01:42:51,800
CALORIES DESPITE BEING MUCH,

3090
01:42:51,800 --> 01:42:53,920
MUCH MORE PHYSICALLY ACTIVE,

3091
01:42:53,920 --> 01:42:55,840
SUGGESTING THAT THEY'RE BURNING

3092
01:42:55,840 --> 01:42:57,360
FEWER CALORIES ON OTHER THINGS.

3093
01:42:57,360 --> 01:42:59,760
PERHAPS THE BIGGEST LOSERS ARE

3094
01:42:59,760 --> 01:43:00,800
ANOTHER EXAMPLE OF THAT, WHO

3095
01:43:00,800 --> 01:43:04,600
HAVE CHRONICALLY RELAXED

3096
01:43:04,600 --> 01:43:06,480
PHYSICAL ACTIVITY OVER A NUMBER

3097
01:43:06,480 --> 01:43:11,480
OF YEAST AND -- UNRELATED TO THE

3098
01:43:11,480 --> 01:43:13,360
NEGATIVE ENERGY BALANCE AND

3099
01:43:13,360 --> 01:43:14,680
WEIGHT LOSS WHICH WE OBSERVED

3100
01:43:14,680 --> 01:43:15,480
EARLY ON.

3101
01:43:15,480 --> 01:43:17,720
>>APROPOS OF THAT, AARON,
I

3102
01:43:17,720 --> 01:43:18,800
GUESS THIS IS REALLY FOR YOU,

3103
01:43:18,800 --> 01:43:22,360
HAVE THERE BEEN STUDIES OF BROWN

3104
01:43:22,360 --> 01:43:28,000
FAT IN NORDIC PEOPLE, PEOPLE WHO

3105
01:43:28,000 --> 01:43:31,880
ARE LIVING UNDER LOWER

3106
01:43:31,880 --> 01:43:34,000
TEMPERATURE CONSISTENTLY AND

3107
01:43:34,000 --> 01:43:35,440
ADAPTING AND, FOR THE MOST PART,

3108
01:43:35,440 --> 01:43:41,800
ON A PRETTY HIGH FAT DIET?

3109
01:43:41,800 --> 01:43:43,640
>>YES, VERY LITTLE HAS
BEEN

3110
01:43:43,640 --> 01:43:45,840
DONE SO FAR BECAUSE IT'S REALLY

3111
01:43:45,840 --> 01:43:48,520
HARD TO MEASURE BROWN FAT

3112
01:43:48,520 --> 01:43:50,600
ACTIVITY IN PEOPLE WHO ARE NOT

3113
01:43:50,600 --> 01:43:55,800
NEAR MRIs OR PET/KRCH T PET/CT .

3114
01:43:55,800 --> 01:43:58,400
SO THE ONLY THING THAT'S BEEN

3115
01:43:58,400 --> 01:44:02,000
DONE IS A STUDY BY STEPHANIE

3116
01:44:02,000 --> 01:44:04,000
LEVY'S GROUP, PEOPLE IN

3117
01:44:04,000 --> 01:44:04,880
NORTHEASTERN RUSSIAN FEDERATION

3118
01:44:04,880 --> 01:44:07,200
OUT IN THE SAHA REGION, AND THEY

3119
01:44:07,200 --> 01:44:11,080
USE INFRARED IMAGING WHICH HAS

3120
01:44:11,080 --> 01:44:12,040
ITS CHALLENGES TO USE, BULL IT

3121
01:44:12,040 --> 01:44:15,840
DID ABUT ITDID APPEAR BASED ON Y

3122
01:44:15,840 --> 01:44:17,000
SHOW IS THERE'S A DIFFERENCE IN

3123
01:44:17,000 --> 01:44:19,320
THE COLD TOLERANCE AND ENERGY

3124
01:44:19,320 --> 01:44:20,200
EXPENDITURE COMPARED TO PEOPLE

3125
01:44:20,200 --> 01:44:20,880
LIVING IN CHICAGO.

3126
01:44:20,880 --> 01:44:21,920
BUT THESE KINDS OF STUDIES NEED

3127
01:44:21,920 --> 01:44:26,480
TO BE REPEATED AND IDEALLY WITH

3128
01:44:26,480 --> 01:44:27,640
THE STATE OF THE ART MEASUREMENT

3129
01:44:27,640 --> 01:44:29,920
SO WE CAN GET BOTH AN ACCURATE

3130
01:44:29,920 --> 01:44:31,040
AND PRECISE ASSESSMENT OF THE

3131
01:44:31,040 --> 01:44:32,760
BROWN ADIPOSE TISSUE AND ENERGY

3132
01:44:32,760 --> 01:44:34,880
EXPENDITURE AND COLD TOLERANCE

3133
01:44:34,880 --> 01:44:36,600
IN COMMUNITIES THAT WOULD HAVE

3134
01:44:36,600 --> 01:44:38,840
SPENT HUNDREDS IF NOT THOUSANDS

3135
01:44:38,840 --> 01:44:40,600
OF YEARS IN COLDER ENVIRONMENTS.

3136
01:44:40,600 --> 01:44:43,480
I WILL SAY THIS, THAT WE HAVE

3137
01:44:43,480 --> 01:44:45,880
STUDIED PEOPLE WHO CAME DIRECTLY

3138
01:44:45,880 --> 01:44:47,840
FROM CENTRAL AFRICA AND

3139
01:44:47,840 --> 01:44:48,800
PARTICIPATED IN THE CLINICAL

3140
01:44:48,800 --> 01:44:51,000
TRIALS WE'VE CONDUCTED AT THE

3141
01:44:51,000 --> 01:44:53,720
NIH AND THOSE AFRICAN MEN HAD A

3142
01:44:53,720 --> 01:44:54,640
LARGE AMOUNT OF BROWN FAT.

3143
01:44:54,640 --> 01:44:56,400
SO I DON'T THINK IT'S AS SIMPLE

3144
01:44:56,400 --> 01:44:58,080
AS SAYING THAT COMMUNITIES THAT

3145
01:44:58,080 --> 01:44:59,800
ARE IN HIGHER LATITUDES WILL

3146
01:44:59,800 --> 01:45:01,520
HAVE MORE BROWN FAT AND MORE

3147
01:45:01,520 --> 01:45:03,040
COLD TOLERANCE, IT'S ACTUALLY

3148
01:45:03,040 --> 01:45:04,920
MORE COMPLICATED AND IT MAY BE

3149
01:45:04,920 --> 01:45:06,200
BECAUSE THEY'RE ALSO -- YOU

3150
01:45:06,200 --> 01:45:07,560
DRESS TO WHAT YOUR ENVIRONMENT

3151
01:45:07,560 --> 01:45:10,040
REQUIRES OF YOU, OR THAT BROWN

3152
01:45:10,040 --> 01:45:11,200
FAT IS INVOLVED IN MORE THAN

3153
01:45:11,200 --> 01:45:14,560
JUST COLD RESPONSE AND HAS OTHER

3154
01:45:14,560 --> 01:45:15,280
RESPONSE EXHIBITS AS WELL.

3155
01:45:15,280 --> 01:45:16,720
SO WE NEED TO SEPARATE THOSE TWO

3156
01:45:16,720 --> 01:45:17,480
AND GET MORE INFORMATION ABOUT

3157
01:45:17,480 --> 01:45:18,760
IT.

3158
01:45:18,760 --> 01:45:21,080
>> I VISITED THE MEDICAL
CENTER

3159
01:45:21,080 --> 01:45:26,480
IN FAIRBANKS ALASKA, WHERE THEY

3160
01:45:26,480 --> 01:45:29,120
HAVE A PET SCAN AND ALL THE

3161
01:45:29,120 --> 01:45:32,880
MODERN EQUIPMENT AND DEAL WITH

3162
01:45:32,880 --> 01:45:34,520
THIS POPULATION, PARTICULARLY

3163
01:45:34,520 --> 01:45:37,360
THE ANOMITE.

3164
01:45:37,360 --> 01:45:39,320
AT ANY RATE.

3165
01:45:39,320 --> 01:45:42,680
KEVIN, WHAT IS ULTRA PROCESSING

3166
01:45:42,680 --> 01:45:43,280
ACTUALLY -- WHAT DOES IT

3167
01:45:43,280 --> 01:45:43,760
INVOLVE?

3168
01:45:43,760 --> 01:45:46,240
IT'S A BIG WORD, IT'S A FANCY

3169
01:45:46,240 --> 01:45:47,800
WORD, BUT WHAT DOES IT MEAN?

3170
01:45:47,800 --> 01:45:49,120
WHAT DO THEY ACTUALLY DO?

3171
01:45:49,120 --> 01:45:51,280
>>YEAH, SO, I MEAN, THERE
ARE A

3172
01:45:51,280 --> 01:45:53,880
WHOLE BUNCH OF REALLY SMART FOOD

3173
01:45:53,880 --> 01:45:55,120
SCIENTISTS AND TECHNOLOGISTS WHO

3174
01:45:55,120 --> 01:45:58,480
HAVE FOUND INGENIUS WAYS TO KIND

3175
01:45:58,480 --> 01:46:01,240
OF EXTRACT INGREDIENTS FROM

3176
01:46:01,240 --> 01:46:03,120
VARIOUS FOOD STUFFS, REPACKAGE

3177
01:46:03,120 --> 01:46:05,120
THEM AND REFORMULATE THEM IN

3178
01:46:05,120 --> 01:46:07,560
DIFFERENT WAYS TO MAKE THEM

3179
01:46:07,560 --> 01:46:09,880
SHELF-STABLE AND LIMIT, YOU

3180
01:46:09,880 --> 01:46:15,640
KNOW, MICROBIAL ASPECTS TO KIND

3181
01:46:15,640 --> 01:46:17,320
OF MAKE VERY SAFE FOODS, MAKE

3182
01:46:17,320 --> 01:46:19,320
THEM CONVENIENT AND INEXPENSIVE,

3183
01:46:19,320 --> 01:46:23,880
AND ESSENTIALLY REFORMULATE FROM

3184
01:46:23,880 --> 01:46:25,640
KIND OF INGREDIENTS THAT ARE NO

3185
01:46:25,640 --> 01:46:27,280
LONGER SORT OF PHYSICALLY

3186
01:46:27,280 --> 01:46:31,120
IDENTIFIABLE WITH THE PLANTS AND

3187
01:46:31,120 --> 01:46:34,440
ANIMALS THAT THEY CAME FROM.

3188
01:46:34,440 --> 01:46:35,680
AND ONE OF THE QUESTIONS IS, WHY

3189
01:46:35,680 --> 01:46:37,560
IS IT THAT THESE FOODS, WHICH

3190
01:46:37,560 --> 01:46:41,920
ARE NOW RELATED IN HUNDREDS OF

3191
01:46:41,920 --> 01:46:43,000
EPIDEMIOLOGICAL STUDIES WITH

3192
01:46:43,000 --> 01:46:46,040
INCREASED RISK FOR OBESITY, TYPE

3193
01:46:46,040 --> 01:46:47,800
2 DIABETES, CARDIOVASCULAR

3194
01:46:47,800 --> 01:46:48,640
DISEASE, MANY FORMS OF CANCER

3195
01:46:48,640 --> 01:46:49,800
AND ALL OF THESE OTHER THINGS,

3196
01:46:49,800 --> 01:46:51,600
WHAT IS IT ABOUT THESE FOODS

3197
01:46:51,600 --> 01:46:53,480
THAT ARE CAUSING THESE PROBLEMS?

3198
01:46:53,480 --> 01:46:54,600
AND MY PARTICULAR INTEREST IS

3199
01:46:54,600 --> 01:46:55,760
WHAT IS IT ABOUT THESE FOODS

3200
01:46:55,760 --> 01:46:58,840
THAT CAUSE PEOPLE TO CLEARLY

3201
01:46:58,840 --> 01:47:01,760
OVEREAT AND GAIN WEIGHT AND GAIN

3202
01:47:01,760 --> 01:47:03,080
BODY FAT DESPITE THEM NOT TRYING

3203
01:47:03,080 --> 01:47:06,600
TO DO SO, EVEN WHEN YOU MATCH

3204
01:47:06,600 --> 01:47:09,120
THE OVERALL DIETS FOR THE

3205
01:47:09,120 --> 01:47:10,920
PRESENTED CALORIES, SALT, SHEUL

3206
01:47:10,920 --> 01:47:15,680
GAR, FAT, AND FIBER, AND

3207
01:47:15,680 --> 01:47:16,480
GLYCEMIC LOAD?

3208
01:47:16,480 --> 01:47:17,760
AND WE DON'T KNOW THE ANSWER.

3209
01:47:17,760 --> 01:47:19,640
THAT'S, I THINK, A GREAT

3210
01:47:19,640 --> 01:47:21,080
MYSTERY, AND I THINK WE NEED --

3211
01:47:21,080 --> 01:47:22,960
GIVEN THAT THESE FOODS NOW MAKE

3212
01:47:22,960 --> 01:47:23,920
UP MORE THAN HALF OF THE U.S.

3213
01:47:23,920 --> 01:47:27,040
FOOD SUPPLY, I THINK WE NEED TO

3214
01:47:27,040 --> 01:47:28,200
KNOW THE ANSWER TO THAT

3215
01:47:28,200 --> 01:47:28,440
QUESTION.

3216
01:47:28,440 --> 01:47:30,480
SO WE HAVE A STUDY ONGOING NOW

3217
01:47:30,480 --> 01:47:32,040
AT THE CLINICAL CENTER WHERE

3218
01:47:32,040 --> 01:47:34,040
WE'VE REFORMULATED THE

3219
01:47:34,040 --> 01:47:35,280
ULTRAPROCESSED DIET IN WAYS THAT

3220
01:47:35,280 --> 01:47:37,760
WE THINK MIGHT MITIGATE THE

3221
01:47:37,760 --> 01:47:41,240
INCREASE IN ENERGY INTAKE, AND I

3222
01:47:41,240 --> 01:47:42,720
THINK THAT WE'LL WAIT AND SEE

3223
01:47:42,720 --> 01:47:44,840
FOR THE RESULTS OF THAT IF WE'RE

3224
01:47:44,840 --> 01:47:45,720
SUCCESSFUL OR NOT.

3225
01:47:45,720 --> 01:47:48,160
BUT WE HAVE DESIGNED THESE NEW

3226
01:47:48,160 --> 01:47:50,560
ULTRAPROCESSED DIETS THAT STILL

3227
01:47:50,560 --> 01:47:54,800
MAINTAIN 80% OF CAL R CALORIES M

3228
01:47:54,800 --> 01:47:56,280
ULTRAPROCESSED FOODS BUT ARE NOW

3229
01:47:56,280 --> 01:47:57,640
BURIED IN OTHER NUTRITIONAL

3230
01:47:57,640 --> 01:47:59,000
PARAMETERS THAT WE THINK WILL

3231
01:47:59,000 --> 01:47:59,720
MITIGATE THOSE PROPERTIES.

3232
01:47:59,720 --> 01:48:01,280
BUT I THINK THAT THIS IS ONE OF

3233
01:48:01,280 --> 01:48:03,040
THE GREAT MYSTERIES, IS THAT

3234
01:48:03,040 --> 01:48:06,760
THERE'S THIS CLEAR SIGNAL THAT

3235
01:48:06,760 --> 01:48:08,640
CONSUMPTION OF THESE FOODS IS

3236
01:48:08,640 --> 01:48:10,680
PROBLEMATIC IN THE EPIDEMIOLOGY.

3237
01:48:10,680 --> 01:48:12,000
THERE'S OUR TRIAL WHICH SHOWS

3238
01:48:12,000 --> 01:48:15,040
THAT THEY SEEM TO CAUSE PEOPLE

3239
01:48:15,040 --> 01:48:16,800
TO CONSUME EXCESS CALORIES.

3240
01:48:16,800 --> 01:48:21,920
WHAT'S THE MECHANISM?

3241
01:48:21,920 --> 01:48:23,280
AND WHAT IS IT ABOUT THESE FOODS

3242
01:48:23,280 --> 01:48:23,800
THAT CAUSES THAT?

3243
01:48:23,800 --> 01:48:25,080
WE JUST DON'T KNOW.

3244
01:48:25,080 --> 01:48:27,280
>>IS THERE A CULTURAL
ELEMENT

3245
01:48:27,280 --> 01:48:28,200
TO IT?

3246
01:48:28,200 --> 01:48:30,200
I MEAN, THE PUBLIC, WE'RE ALL

3247
01:48:30,200 --> 01:48:32,840
SUBJECTED THROUGH ADVERTISING

3248
01:48:32,840 --> 01:48:34,960
AND EVERYTHING ELSE OF THESE

3249
01:48:34,960 --> 01:48:36,680
THINGS THAT NOT ONLY LOOK GOOD,

3250
01:48:36,680 --> 01:48:40,200
THEY TASTE GOOD, AND ALWAYS, THE

3251
01:48:40,200 --> 01:48:41,840
ACTORS AND ACTRESSES ARE USUALLY

3252
01:48:41,840 --> 01:48:44,720
SLIM AND TRIM AND VERY ACTIVE

3253
01:48:44,720 --> 01:48:45,080
AND SO FORTH.

3254
01:48:45,080 --> 01:48:46,280
IS THERE A CULTURAL THING?

3255
01:48:46,280 --> 01:48:49,880
IF YOU INTRODUCED A PROCESSED

3256
01:48:49,880 --> 01:48:51,520
FOOD THING AMONGST THE

3257
01:48:51,520 --> 01:48:53,920
POPULATION THAT'S NOT EXPOSED TO

3258
01:48:53,920 --> 01:48:55,160
THOSE CULTURAL THINGS, I DON'T

3259
01:48:55,160 --> 01:48:57,400
KNOW, MAYBE THAT'S IMPOSSIBLE,

3260
01:48:57,400 --> 01:48:57,600
BUT --

3261
01:48:57,600 --> 01:48:59,760
>>THIS IS ACTUALLY ONE OF
THE

3262
01:48:59,760 --> 01:49:02,520
THINGS THAT FOLKS LIKE CARLOS

3263
01:49:02,520 --> 01:49:04,600
MONTERO IN BRAZIL WERE CONCERNED

3264
01:49:04,600 --> 01:49:05,920
ABOUT, BECAUSE IN THEIR COUNTRY,

3265
01:49:05,920 --> 01:49:09,080
WHEN HE INTRODUCED THE NOVA

3266
01:49:09,080 --> 01:49:10,040
CLASSIFICATION SYSTEM, MUCH,

3267
01:49:10,040 --> 01:49:11,640
MUCH LOWER PROPORTION OF THE

3268
01:49:11,640 --> 01:49:14,200
FOOD SUPPLY WAS COMING FROM

3269
01:49:14,200 --> 01:49:15,360
ULTRAPROCESSED FOODS, AND YET

3270
01:49:15,360 --> 01:49:16,960
ONE OF THE THINGS THAT HAS BEEN

3271
01:49:16,960 --> 01:49:20,080
CLEAR IS SOMETHING THAT BARRY

3272
01:49:20,080 --> 01:49:21,680
POPKIN IN NORTH CAROLINA HAS

3273
01:49:21,680 --> 01:49:23,120
MENTIONED AS DIFFERENT CULTURES

3274
01:49:23,120 --> 01:49:25,120
UNDERGO WHAT'S CALLED THE

3275
01:49:25,120 --> 01:49:25,880
NUTRITION TRANSITION, AS THEY

3276
01:49:25,880 --> 01:49:27,280
BECOME RICH ENOUGH TO START TO

3277
01:49:27,280 --> 01:49:29,160
KIND OF MOVE OUT OF POVERTY AND

3278
01:49:29,160 --> 01:49:32,400
AFFORD THE KINDS OF LIFESTYLE

3279
01:49:32,400 --> 01:49:33,760
THAT WE IN THE WEST ARE

3280
01:49:33,760 --> 01:49:35,760
FORTUNATE ENOUGH TO HAVE, ONE OF

3281
01:49:35,760 --> 01:49:36,880
THE THINGS THAT THEY DO IS THEY

3282
01:49:36,880 --> 01:49:40,320
CHANGE THEIR DIETS QUITE

3283
01:49:40,320 --> 01:49:40,640
DRAMATICALLY.

3284
01:49:40,640 --> 01:49:42,200
THE LOWER AMOUNTS OF THEIR

3285
01:49:42,200 --> 01:49:44,480
INCOME IS SPENT ON FOODS AND

3286
01:49:44,480 --> 01:49:47,040
THOSE FOODS BECOME RELATIVELY

3287
01:49:47,040 --> 01:49:49,760
ACCESSIBLE AND EASIER TO EAT.

3288
01:49:49,760 --> 01:49:51,520
AND SO EVEN IN THOSE COUNTRIES,

3289
01:49:51,520 --> 01:49:53,360
WE SEE THAT THE INCREASE -- AS

3290
01:49:53,360 --> 01:49:54,880
ULTRAPROCESSED FOODS INCREASE,

3291
01:49:54,880 --> 01:49:58,560
THERE IS A CORRELATION WITH

3292
01:49:58,560 --> 01:50:00,240
INCREASING RATES OF OBESITY AND

3293
01:50:00,240 --> 01:50:01,480
EVEN WITHIN THE POPULATIONS, YOU

3294
01:50:01,480 --> 01:50:04,960
CAN LOOK AT A CORRELATION

3295
01:50:04,960 --> 01:50:07,440
BETWEEN -- IN PROSPECTIVE

3296
01:50:07,440 --> 01:50:08,840
LONGITUDINAL STUDIES AS WELL AS

3297
01:50:08,840 --> 01:50:09,840
CROSS-SECTIONAL STUDIES, THOSE

3298
01:50:09,840 --> 01:50:11,600
WHO EAT MORE ULTRAPROCESSED

3299
01:50:11,600 --> 01:50:13,080
FOODS TEND TO HAVE GREATER RATES

3300
01:50:13,080 --> 01:50:14,080
OF EE BEES IT.

3301
01:50:14,080 --> 01:50:15,680
AGAIN, WHY, WE DON'T KNOW.

3302
01:50:15,680 --> 01:50:17,000
THE GOAL WOULD BE TO FIGURE OUT

3303
01:50:17,000 --> 01:50:19,240
WHAT THE MECHANISM IS SO WE CAN

3304
01:50:19,240 --> 01:50:20,600
INFORM PRODUCT REFORMULATIONS

3305
01:50:20,600 --> 01:50:22,280
AND FOREIGN POLICY MAKERS TO

3306
01:50:22,280 --> 01:50:23,880
WHAT THE REAL PROBLEMS ARE.

3307
01:50:23,880 --> 01:50:25,360
WHEN YOU HAVE A SYSTEM RIGHT NOW

3308
01:50:25,360 --> 01:50:28,840
LIKE THE NOVA SYSTEM THAT

3309
01:50:28,840 --> 01:50:29,440
BASICALLY DEMONIZES MORE THAN

3310
01:50:29,440 --> 01:50:32,920
HALF OF THE FOOD SUPPLY, IT'S

3311
01:50:32,920 --> 01:50:35,400
NOT A VIABLE RECOMMENDATION TO

3312
01:50:35,400 --> 01:50:37,160
JUST CUT HALF OF THE FOOD SUPPLY

3313
01:50:37,160 --> 01:50:38,000
OUT OF THE FOOD SUPPLY.

3314
01:50:38,000 --> 01:50:39,600
YOU HAVE TO BETTER UNDERSTAND

3315
01:50:39,600 --> 01:50:42,240
WHAT THE PROBLEMS ARE IN ORDER

3316
01:50:42,240 --> 01:50:43,640
TO ADDRESS THEM, EITHER WITH

3317
01:50:43,640 --> 01:50:47,760
POLICY OR WITH REFORMULATIONS.

3318
01:50:47,760 --> 01:50:49,720
>>STUDIES OF THE TYPE
THAT

3319
01:50:49,720 --> 01:50:51,840
EITHER OF YOU DESCRIBE BEEN

3320
01:50:51,840 --> 01:50:55,560
PERFORMED IN NATIVE AMERICAN

3321
01:50:55,560 --> 01:50:57,440
POPULATIONS, PARTICULARLY THOSE

3322
01:50:57,440 --> 01:50:59,200
LIVING ON A RESERVATION WHERE

3323
01:50:59,200 --> 01:51:02,680
THE AVAILABILITY OF FRESH

3324
01:51:02,680 --> 01:51:04,480
FOODS IS PROFOUNDLY LIMITED AND

3325
01:51:04,480 --> 01:51:08,120
IN SOME INSTANCES, THERE IS

3326
01:51:08,120 --> 01:51:11,280
ACTUALLY GOVERNMENT SUPPORT FOR

3327
01:51:11,280 --> 01:51:13,800
FAST FOODS.

3328
01:51:13,800 --> 01:51:14,800
HAVE THOSE POPULATIONS BEEN

3329
01:51:14,800 --> 01:51:17,000
STUDIED FROM THE STANDPOINT OF

3330
01:51:17,000 --> 01:51:18,400
THE ISSUES THAT BOTH OF YOU DEAL

3331
01:51:18,400 --> 01:51:23,680
WITH?

3332
01:51:23,680 --> 01:51:26,040
>>I CERTAINLY KNOW OUR

3333
01:51:26,040 --> 01:51:29,360
COLLEAGUES IN PHOENIX AT THE

3334
01:51:29,360 --> 01:51:31,680
NIDDK BRANCH OUT THERE STUDIED

3335
01:51:31,680 --> 01:51:32,360
THEM EXTENSIVELY.

3336
01:51:32,360 --> 01:51:34,360
I DON'T KNOW THAT THEY'VE LOOKED

3337
01:51:34,360 --> 01:51:35,720
AT ULTRAPROCESSED FOODS BUT

3338
01:51:35,720 --> 01:51:37,240
THEY'VE CERTAINLY MEASURED

3339
01:51:37,240 --> 01:51:38,640
VARIOUS ASPECTS OF ENERGY

3340
01:51:38,640 --> 01:51:40,920
METABOLISM AND FOOD INTAKE, AND

3341
01:51:40,920 --> 01:51:42,960
AARON MIGHT BE FAMILIAR WITH ANY

3342
01:51:42,960 --> 01:51:43,960
BROWN ADIPOSE TISSUE STUDIES,

3343
01:51:43,960 --> 01:51:47,160
BUT I'M NOT AWARE OF -- IF

3344
01:51:47,160 --> 01:51:49,360
THEY'VE FOCUSED ON THAT.

3345
01:51:49,360 --> 01:51:52,840
>>BOTH OF YOU -- GO
AHEAD,

3346
01:51:52,840 --> 01:51:53,120
AARON.

3347
01:51:53,120 --> 01:51:54,800
>>I WAS GOING TO SUPPORT
WHAT

3348
01:51:54,800 --> 01:51:56,400
KEVIN JUST SAID, THAT OUR

3349
01:51:56,400 --> 01:51:58,120
COLLEAGUES HAVE DONE SOME VERY

3350
01:51:58,120 --> 01:52:04,160
EXTENSIVE STUDIES LOOKING AT THE

3351
01:52:04,160 --> 01:52:04,680
PIMA INDIANS.

3352
01:52:04,680 --> 01:52:06,800
THERE WAS A PAPER PUBLISHED LIKE

3353
01:52:06,800 --> 01:52:08,480
30 YEARS AGO SHOWING THAT THEIR

3354
01:52:08,480 --> 01:52:10,120
DIETS HAVE CHANGED AND THAT

3355
01:52:10,120 --> 01:52:12,720
MIGHT BE ASSOCIATED WITH THE

3356
01:52:12,720 --> 01:52:14,360
HIGH RATES OF OBESITY AND

3357
01:52:14,360 --> 01:52:17,920
DIABETES THAT ARE SEEN IN THOSE

3358
01:52:17,920 --> 01:52:19,400
POPULATIONS, BUT NOT

3359
01:52:19,400 --> 01:52:20,160
SPECIFICALLY ULTRAPROCESSED

3360
01:52:20,160 --> 01:52:21,600
FOODS PER SE AS OPPOSED TO THE

3361
01:52:21,600 --> 01:52:23,000
KINDS OF DETAILED STUDIES THAT

3362
01:52:23,000 --> 01:52:24,640
KEVIN IS CONDUCTING.

3363
01:52:24,640 --> 01:52:27,440
>> HMMM.

3364
01:52:27,440 --> 01:52:30,680
THAT'S INTERESTING.

3365
01:52:30,680 --> 01:52:33,600
SO IS A KETOGENIC DIET -- DOES

3366
01:52:33,600 --> 01:52:36,520
IT HAVE ANY ADVANTAGES AS A

3367
01:52:36,520 --> 01:52:37,040
DIET, PER SE?

3368
01:52:37,040 --> 01:52:38,280
WHAT ARE YOUR COMMENTS?

3369
01:52:38,280 --> 01:52:40,920
THAT SEEMS TO BE ALMOST THE

3370
01:52:40,920 --> 01:52:43,280
LATEST RAGE.

3371
01:52:43,280 --> 01:52:45,840
>>SO THE STUDY THAT I
SHOWED

3372
01:52:45,840 --> 01:52:48,840
WITH THE VERY LOW CARBOHYDRATE,

3373
01:52:48,840 --> 01:52:51,120
HIGH FAT DIET, THAT WAS A

3374
01:52:51,120 --> 01:52:52,160
KETOGENIC DIET.

3375
01:52:52,160 --> 01:52:54,160
THERE ARE VERY HEALTHY VERSIONS

3376
01:52:54,160 --> 01:52:57,560
OF KETOGENIC DIETS AND WE TRIED

3377
01:52:57,560 --> 01:52:58,600
TO EMULATE A VERY HEALTHY

3378
01:52:58,600 --> 01:52:59,600
VERSION IN OUR STUDY.

3379
01:52:59,600 --> 01:53:00,920
IN TERMS OF WEIGHT LOSS, A LOT

3380
01:53:00,920 --> 01:53:03,320
OF PEOPLE EXPERIENCE, YOU KNOW,

3381
01:53:03,320 --> 01:53:05,400
GREAT SUCCESS WITH THOSE DIETS.

3382
01:53:05,400 --> 01:53:07,040
BUT A LOT OF PEOPLE ALSO

3383
01:53:07,040 --> 01:53:07,880
EXPERIENCE GREAT SUCCESS WITH

3384
01:53:07,880 --> 01:53:09,440
THE KIND OF DIET THAT WE TESTED

3385
01:53:09,440 --> 01:53:11,720
IT AGAINST, WHICH WAS A VERY LOW

3386
01:53:11,720 --> 01:53:14,880
FAT PLANT-BASED DIET.

3387
01:53:14,880 --> 01:53:16,880
AND SO THE QUESTION IS WHY, WHY

3388
01:53:16,880 --> 01:53:19,320
ARE SOME PEOPLE MORE SUCCESSFUL

3389
01:53:19,320 --> 01:53:21,240
ON ONE DIET VERSUS ANOTHER, IS

3390
01:53:21,240 --> 01:53:23,960
IT SOMETHING ABOUT THE DIETS,

3391
01:53:23,960 --> 01:53:28,440
PER SE, INTERACTION BETWEEN

3392
01:53:28,440 --> 01:53:31,800
THEIR PARTICULAR BIOLOGY AND THE

3393
01:53:31,800 --> 01:53:33,400
DIETS OR SOCIAL SUPPORT SYSTEMS,

3394
01:53:33,400 --> 01:53:34,400
THEY WERE AT THE RIGHT PLACE AT

3395
01:53:34,400 --> 01:53:37,680
THE RIGHT TIME IN THEIR LIFE TO

3396
01:53:37,680 --> 01:53:40,400
MAKE THAT CHANGE MORE ADHERENT

3397
01:53:40,400 --> 01:53:41,800
AS OPPOSED TO THE LAST TIME THEY

3398
01:53:41,800 --> 01:53:43,120
TRIED A DIFFERENT DIET, WHERE

3399
01:53:43,120 --> 01:53:49,320
THEY WERE UNDERGOING SOME SOCIAL

3400
01:53:49,320 --> 01:53:50,800
UPHEAVAL LIKE LOSING A JOB,

3401
01:53:50,800 --> 01:53:51,720
GOING THROUGH DIVORCE, SOMETHING

3402
01:53:51,720 --> 01:53:53,560
LIKE THAT.

3403
01:53:53,560 --> 01:53:56,760
SOME PEOPLE SEEM TO HAVE GREAT

3404
01:53:56,760 --> 01:53:58,240
SUCCESS ON SOME DIETS WHILE

3405
01:53:58,240 --> 01:53:58,760
OTHERS DON'T.

3406
01:53:58,760 --> 01:54:01,360
WHAT WE DO KNOW IS THIS

3407
01:54:01,360 --> 01:54:02,720
FUNDAMENTAL BIOLOGY THAT RESISTS

3408
01:54:02,720 --> 01:54:04,400
WEIGHT CHANGE SEEMS TO BE

3409
01:54:04,400 --> 01:54:05,400
RELEVANT ON ALL OF THESE

3410
01:54:05,400 --> 01:54:06,400
DIFFERENT KINDS OF DIETS.

3411
01:54:06,400 --> 01:54:07,440
ONE OF THE ADVANTAGES OF THE

3412
01:54:07,440 --> 01:54:09,440
KINDS OF STUDIES THAT WE DO IS

3413
01:54:09,440 --> 01:54:11,440
THAT WE DON'T ALLOW PEOPLE TO

3414
01:54:11,440 --> 01:54:12,800
CHEAT, RIGHT?

3415
01:54:12,800 --> 01:54:15,120
WE ESSENTIALLY COMPLETELY TAKE

3416
01:54:15,120 --> 01:54:15,880
OVER THEIR FOOD ENVIRONMENT.

3417
01:54:15,880 --> 01:54:17,080
THEY HAVE NO ACCESS TO FOODS

3418
01:54:17,080 --> 01:54:19,160
THAT ARE NOT PART OF THE

3419
01:54:19,160 --> 01:54:19,680
KETOGENIC DIET.

3420
01:54:19,680 --> 01:54:20,880
THEY HAVE NO ACCESS TO FOODS

3421
01:54:20,880 --> 01:54:24,840
THAT ARE NOT PART OF THE PLANT

3422
01:54:24,840 --> 01:54:26,640
BASED LOW FAT DIET OR THEY DON'T

3423
01:54:26,640 --> 01:54:28,160
HAVE ACCESS TO FOODS THAT ARE

3424
01:54:28,160 --> 01:54:30,280
NOT PART OF THE UNPROCESSED

3425
01:54:30,280 --> 01:54:31,280
DIET.

3426
01:54:31,280 --> 01:54:33,720
AND SO WHEN YOU TAKE AWAY THOSE

3427
01:54:33,720 --> 01:54:35,280
FACTORS, THOSE OTHER INFLUENCES

3428
01:54:35,280 --> 01:54:36,240
IN THE FOOD ENVIRONMENT AND THE

3429
01:54:36,240 --> 01:54:38,080
ABILITY TO KIND OF CHEAT ON YOUR

3430
01:54:38,080 --> 01:54:39,240
DIETS, WHAT WE SEE ARE THESE

3431
01:54:39,240 --> 01:54:42,080
KIND OF VERY PROFOUND EFFECTS ON

3432
01:54:42,080 --> 01:54:44,360
ENERGY INTAKE AND BODY WEIGHT

3433
01:54:44,360 --> 01:54:45,240
CHANGE WHEN PEOPLE AREN'T EVEN

3434
01:54:45,240 --> 01:54:47,000
TRYING TO CHANGE THEIR BODY

3435
01:54:47,000 --> 01:54:47,840
WEIGHT, WHICH I THINK IS PRETTY

3436
01:54:47,840 --> 01:54:48,200
INTERESTING.

3437
01:54:48,200 --> 01:54:49,400
AND IF WE COULD BETTER

3438
01:54:49,400 --> 01:54:50,600
UNDERSTAND WHAT ARE THE FACTORS

3439
01:54:50,600 --> 01:54:55,040
IN OUR FOOD ENVIRONMENT THAT ARE

3440
01:54:55,040 --> 01:54:56,120
RESULTING IN JUST THESE SHIFTS

3441
01:54:56,120 --> 01:54:58,240
IN THE BIOLOGY OF WHERE OUR

3442
01:54:58,240 --> 01:54:59,920
APPETITE CURVE IS SITTING, THEN

3443
01:54:59,920 --> 01:55:03,040
WE WOULD GO A LONG WAY TO BETTER

3444
01:55:03,040 --> 01:55:03,880
UNDERSTANDING, NUMBER ONE, WHY

3445
01:55:03,880 --> 01:55:05,360
WE HAVE AN OBESITY EPIDEMIC IN

3446
01:55:05,360 --> 01:55:06,520
THE FIRST PLACE, AND NUMBER TWO,

3447
01:55:06,520 --> 01:55:08,080
WHAT WE COULD DO TO ACTUALLY DO

3448
01:55:08,080 --> 01:55:09,240
SOMETHING ABOUT IT, AND WHY SOME

3449
01:55:09,240 --> 01:55:10,880
PEOPLE MIGHT BE MORE SUCCESSFUL

3450
01:55:10,880 --> 01:55:14,200
ON ONE DIET VERSUS ANOTHER.

3451
01:55:14,200 --> 01:55:18,760
>>IS OVEREATING AN
ADDICTION?

3452
01:55:18,760 --> 01:55:24,040
>>I THINK THE WORD
ADDICTION IS

3453
01:55:24,040 --> 01:55:25,600
USED OUTSIDE MY FIELD OF

3454
01:55:25,600 --> 01:55:26,080
EXPERTISE.

3455
01:55:26,080 --> 01:55:28,440
I AM NOT AN ADDICTION SCIENTIST,

3456
01:55:28,440 --> 01:55:32,840
AND SO I WOULD NOT CHARACTERIZE

3457
01:55:32,840 --> 01:55:34,680
IT THAT WAY WITHOUT MUCH BETTER

3458
01:55:34,680 --> 01:55:35,040
UNDERSTANDING.

3459
01:55:35,040 --> 01:55:38,080
IT'S CERTAINLY TRUE THAT THE

3460
01:55:38,080 --> 01:55:39,200
REGIONS OF THE BRAIN THAT HAVE

3461
01:55:39,200 --> 01:55:40,440
BEEN IMPLICATED IN BOTH

3462
01:55:40,440 --> 01:55:42,880
ADDICTION TO DRUGS OF ABUSE WERE

3463
01:55:42,880 --> 01:55:48,520
PROBABLY NATURALLY FORMED TO

3464
01:55:48,520 --> 01:55:50,720
KIND OF MOTIVATE BEHAVIORS THAT

3465
01:55:50,720 --> 01:55:52,240
ARE IMPORTANT FOR PROPAGATION OF

3466
01:55:52,240 --> 01:55:53,040
THE SPECIES.

3467
01:55:53,040 --> 01:55:54,360
THINGS LIKE SEX AND THINGS LIKE,

3468
01:55:54,360 --> 01:56:00,360
YOU KNOW, EATING AND SO I DON'T

3469
01:56:00,360 --> 01:56:03,920
THINK THAT THERE'S MUCH EVIDENCE

3470
01:56:03,920 --> 01:56:09,120
THAT FOOD INTA INIS ADDICTIVE IE

3471
01:56:09,120 --> 01:56:10,360
SAME WAY A DRUG OF ABUSE IS, BUT

3472
01:56:10,360 --> 01:56:12,360
IT CERTAINLY SEEMS LIKE SOME OF

3473
01:56:12,360 --> 01:56:13,760
THE NEUROBIOLOGY MIGHT BE IN

3474
01:56:13,760 --> 01:56:16,680
COMMON BETWEEN THE TWO THINGS.

3475
01:56:16,680 --> 01:56:19,480
>>SO SPEAKING OF
NEUROBIOLOGY

3476
01:56:19,480 --> 01:56:24,120
AND ADDICTION, I READ -- TO

3477
01:56:24,120 --> 01:56:26,640
PREPARE A LITTLE BIT, I READ

3478
01:56:26,640 --> 01:56:29,040
ABOUT CANNABINOIDS AND THE FACT

3479
01:56:29,040 --> 01:56:31,640
THAT APPARENTLY THERE ARE

3480
01:56:31,640 --> 01:56:33,120
RECEPTORS IN BOTH WHITE FAT AND

3481
01:56:33,120 --> 01:56:36,440
BROWN FAT.

3482
01:56:36,440 --> 01:56:38,760
AND NOW THAT IT SEEMS AS IF

3483
01:56:38,760 --> 01:56:41,040
CANNABINOIDS ARE BEING

3484
01:56:41,040 --> 01:56:43,200
INTRODUCED INTO GENERAL LIFE FOR

3485
01:56:43,200 --> 01:56:48,280
AN AWFUL LOT OF PEOPLE, I GUESS

3486
01:56:48,280 --> 01:56:50,240
IT'S APPROPRIATE TO ASK WHAT

3487
01:56:50,240 --> 01:56:51,920
THEIR EFFECT IS, DO WE KNOW, ON

3488
01:56:51,920 --> 01:56:55,480
THE BROWN FAT POPULATION, IT'S

3489
01:56:55,480 --> 01:56:57,800
SIZE OR ITS ACTIVITY, IS THERE

3490
01:56:57,800 --> 01:56:59,600
SOMETHING THAT SHUL HAVE SOME

3491
01:56:59,600 --> 01:57:05,120
CONCERN OR INTEREST IN?

3492
01:57:05,120 --> 01:57:05,320
AARON?

3493
01:57:05,320 --> 01:57:08,600
>>YES.

3494
01:57:08,600 --> 01:57:11,120
THERE ARE RECEPTORS AND THERE IS

3495
01:57:11,120 --> 01:57:14,720
RESEARCH IN THIS AREA, SOME OF

3496
01:57:14,720 --> 01:57:16,160
WHICH I'M ACTUALLY REVIEWING SO

3497
01:57:16,160 --> 01:57:17,800
I CAN'T COMMENT TOO MUCH ABOUT

3498
01:57:17,800 --> 01:57:24,600
IT, BUT I WILL SAY THAT AT THE

3499
01:57:24,600 --> 01:57:27,200
GLOBAL LEVEL, CLEARLY THERE'S AN

3500
01:57:27,200 --> 01:57:31,240
IMPACT OF CANNABINOIDS ON

3501
01:57:31,240 --> 01:57:32,400
APPETITE, AND THAT BLOCKING

3502
01:57:32,400 --> 01:57:35,840
THOSE SIGNALS CAN LEAD TO SOME

3503
01:57:35,840 --> 01:57:38,480
WEIGHT LOSS BUT CAUSES A LOT OF

3504
01:57:38,480 --> 01:57:39,680
OTHER EFFECTS THAT, THEREFORE,

3505
01:57:39,680 --> 01:57:41,320
MAKE IT DIFFICULT TO DEVELOP A

3506
01:57:41,320 --> 01:57:42,640
PHARMACEUTICAL AGENT BASED ON

3507
01:57:42,640 --> 01:57:45,000
THOSE SIGNALING PATHWAYS TO BE

3508
01:57:45,000 --> 01:57:47,920
AVAILABLE IN THE MARKET

3509
01:57:47,920 --> 01:57:48,440
CURRENTLY.

3510
01:57:48,440 --> 01:57:50,400
CAN SPECIFIC CANNABINOID

3511
01:57:50,400 --> 01:57:53,960
RECEPTORS, CAN THEY CAUSE BROWN

3512
01:57:53,960 --> 01:57:55,160
ADIPOCYTE PROLIFERATION THAT IS

3513
01:57:55,160 --> 01:57:57,680
STILL BEING INVESTIGATED AND

3514
01:57:57,680 --> 01:57:59,160
IT'S A DISTINCT POSSIBILITY AND

3515
01:57:59,160 --> 01:57:59,880
HOPEFULLY WE'LL GET MORE CLARITY

3516
01:57:59,880 --> 01:58:01,600
ON THAT OVER THE NEXT FEW MONTHS

3517
01:58:01,600 --> 01:58:02,120
AND YEARS.

3518
01:58:02,120 --> 01:58:05,160
>>GOOD.

3519
01:58:05,160 --> 01:58:07,720
SO WOULD EITHER OF YOU LIKE TO

3520
01:58:07,720 --> 01:58:08,600
COMMENT ABOUT THE -- WHAT SEEMS

3521
01:58:08,600 --> 01:58:15,040
TO BE THE CURRENT FOCUS PUBLIC

3522
01:58:15,040 --> 01:58:17,520
ATTENTION, AND THAT'S THE NEW

3523
01:58:17,520 --> 01:58:20,640
TYPES OF DRUGS THAT ARE BEING

3524
01:58:20,640 --> 01:58:24,720
PROMOTED FOR CONTROL OF DIABETES

3525
01:58:24,720 --> 01:58:26,560
AND PEOPLE SEEM TO LOSE A

3526
01:58:26,560 --> 01:58:28,200
TREMENDOUS AMOUNT OF WEIGHT

3527
01:58:28,200 --> 01:58:36,320
WHILE THEY'RE TAKING THESE DRU 

3528
01:58:36,320 --> 01:58:36,520
DRUGS.

3529
01:58:36,520 --> 01:58:38,000
DO WE REALLY UNDERSTAND HOW

3530
01:58:38,000 --> 01:58:38,920
THAT'S HAPPENING OR WHAT ARE

3531
01:58:38,920 --> 01:58:39,880
YOUR THOUGHTS ABOUT IT?

3532
01:58:39,880 --> 01:58:41,840
KEVIN, DO YOU WANT TO COMMENT ON

3533
01:58:41,840 --> 01:58:42,520
THAT?

3534
01:58:42,520 --> 01:58:43,160
>>SURE.

3535
01:58:43,160 --> 01:58:45,880
I MEAN, I THINK THAT, YES, IT'S

3536
01:58:45,880 --> 01:58:49,080
A VERY EXCITING TIME TO BE IN

3537
01:58:49,080 --> 01:58:50,520
OBESITY SCIENCE, AND THE FACT

3538
01:58:50,520 --> 01:58:54,560
THAT THERE ARE THESE DRUGS THAT

3539
01:58:54,560 --> 01:58:56,160
ARE MIM MIBGING VERY HIGH LEVELS

3540
01:58:56,160 --> 01:59:02,000
OF GLP1, WHICH IS AN ENDOCRINE

3541
01:59:02,000 --> 01:59:03,520
HORMONE, THESE DRUGS BASICALLY

3542
01:59:03,520 --> 01:59:08,960
ARE LONG-ACTING VERSIONS OF GLPR

3543
01:59:08,960 --> 01:59:11,040
MUCH LONGER THAN IS

3544
01:59:11,040 --> 01:59:12,840
PHYSIOLOGICALLY NORMAL AFTER

3545
01:59:12,840 --> 01:59:14,040
MEALS AND CAN REACH VERY HIGH

3546
01:59:14,040 --> 01:59:17,880
LEVELS AND AS A RESULT, DECREASE

3547
01:59:17,880 --> 01:59:18,680
PEOPLE'S APPETITE BY WAYS THAT

3548
01:59:18,680 --> 01:59:20,440
ARE NOT COMPLETELY UNDERSTOOD,

3549
01:59:20,440 --> 01:59:21,960
ALTHOUGH A LOT OF THE

3550
01:59:21,960 --> 01:59:24,040
NEUROBIOLOGY IS BEGINNING TO BE

3551
01:59:24,040 --> 01:59:25,640
UNCOVERED, BUT THAT SEEMS TO BE

3552
01:59:25,640 --> 01:59:27,080
THE PRIMARY WAY THAT THEY WORK

3553
01:59:27,080 --> 01:59:30,560
IN HUMANS AS OPPOSED TO CHANG CE

3554
01:59:30,560 --> 01:59:32,080
IN CALORIE EXPENDITURE, FOR

3555
01:59:32,080 --> 01:59:33,080
EXAMPLE, ALTHOUGH I THINK THAT

3556
01:59:33,080 --> 01:59:34,640
THERE IS SOME OPEN QUESTIONS IN

3557
01:59:34,640 --> 01:59:36,440
THAT REGARD, WHETHER OR NOT THEY

3558
01:59:36,440 --> 01:59:39,960
CAN HELP PREVENT SOME OF THE

3559
01:59:39,960 --> 01:59:41,400
SLOWING OF METABOLISM THAT

3560
01:59:41,400 --> 01:59:42,200
OCCURS I THINK WITH WEIGHT LOSS

3561
01:59:42,200 --> 01:59:43,640
IS STILL A LITTLE BIT OF AN OPEN

3562
01:59:43,640 --> 01:59:44,480
QUESTION, BUT IT'S CLEAR THAT

3563
01:59:44,480 --> 01:59:45,880
THE PRIMARY REASON THAT THEY

3564
01:59:45,880 --> 01:59:48,400
WORK IS THEY DECREASE PEOPLE'S

3565
01:59:48,400 --> 01:59:48,800
APPETITE.

3566
01:59:48,800 --> 01:59:50,680
HOW THAT EXACTLY WORKS AND WHAT

3567
01:59:50,680 --> 01:59:54,480
PARTICULAR AREAS OF THE BRAIN,

3568
01:59:54,480 --> 01:59:55,720
HINDBRAIN IS IMPORTANT,

3569
01:59:55,720 --> 01:59:56,760
HYPOTHALAMUS IS IMPORTANT, BUT I

3570
01:59:56,760 --> 01:59:58,400
DON'T THINK WE KNOW IN HUMANS

3571
01:59:58,400 --> 01:59:59,920
EXACTLY THE RELATIVE ROLE OF

3572
01:59:59,920 --> 02:00:03,480
BOTH OF THOSE BRAIN REGIONS.

3573
02:00:03,480 --> 02:00:08,480
>>SO YOUR STUDIES FOCUSED
ON

3574
02:00:08,480 --> 02:00:10,640
PEOPLE WHOM AS YOU SAY YOU'RE

3575
02:00:10,640 --> 02:00:11,240
CONTROLLING EVERYTHING THAT'S

3576
02:00:11,240 --> 02:00:13,800
GOING IN AND COMING OUT AND SO

3577
02:00:13,800 --> 02:00:18,400
FORTH.

3578
02:00:18,400 --> 02:00:20,440
BUT YOU'RE FOCUSING ON DIET AND

3579
02:00:20,440 --> 02:00:21,520
CALORIES.

3580
02:00:21,520 --> 02:00:24,080
SO SUPPOSE IF EXERCISE IS ADDED

3581
02:00:24,080 --> 02:00:26,600
ON TOP OF THAT, IS THERE SOME

3582
02:00:26,600 --> 02:00:28,720
SYNERGISTIC RELATIONSHIP, AND IF

3583
02:00:28,720 --> 02:00:30,520
SO, HOW DOES THAT WORK?

3584
02:00:30,520 --> 02:00:32,040
AND YOU MIGHT WONDER HOW IT

3585
02:00:32,040 --> 02:00:33,120
WORKS WITH THE BROWN FAT AS

3586
02:00:33,120 --> 02:00:35,320
WELL.

3587
02:00:35,320 --> 02:00:36,760
>>EXERCISE IS REALLY

3588
02:00:36,760 --> 02:00:37,160
INTERESTING.

3589
02:00:37,160 --> 02:00:39,280
YOU KNOW, WE DO HAVE OUR FOLKS

3590
02:00:39,280 --> 02:00:40,680
DO A MANDATORY AMOUNT OF

3591
02:00:40,680 --> 02:00:41,960
EXERCISE EVERY DAY, JUST SO THAT

3592
02:00:41,960 --> 02:00:43,160
THEY DON'T BECOME COMPLETELY

3593
02:00:43,160 --> 02:00:44,440
SEDENTARY AND WE CAN MIMIC THE

3594
02:00:44,440 --> 02:00:46,160
SORT OF PHYSICAL OVERALL

3595
02:00:46,160 --> 02:00:47,520
PHYSICAL ACTIVITY LEVEL OF FREE

3596
02:00:47,520 --> 02:00:49,800
LIVING FOLKS.

3597
02:00:49,800 --> 02:00:52,640
AND OF COURSE IN THE BIGGEST

3598
02:00:52,640 --> 02:00:53,520
LOSER FOLKS, THEY DID AN

3599
02:00:53,520 --> 02:00:54,600
ENORMOUS AMOUNT OF EXERCISE.

3600
02:00:54,600 --> 02:00:55,640
ONE OF THE THINGS THAT I THINK

3601
02:00:55,640 --> 02:00:56,920
IS INTERESTING IS THAT DURING

3602
02:00:56,920 --> 02:00:58,920
PERIODS OF WEIGHT LOSS, THE

3603
02:00:58,920 --> 02:01:00,720
EXERCISE EFFECT IS ACTUALLY

3604
02:01:00,720 --> 02:01:02,160
PRETTY MINIMAL COMPARED TO THE

3605
02:01:02,160 --> 02:01:05,800
EFFECT OF THE DIET CHANGE.

3606
02:01:05,800 --> 02:01:07,920
WHEREAS THINGS KIND OF FLIP

3607
02:01:07,920 --> 02:01:09,560
AFTER MANY, MANY YEARS AND LIKE

3608
02:01:09,560 --> 02:01:11,360
I SHOWED WITH THE BIGGEST LOSER

3609
02:01:11,360 --> 02:01:12,680
FOLKS BUT MANY OTHER PEOPLE HAVE

3610
02:01:12,680 --> 02:01:15,480
SHOWN THIS BEFORE, EXERCISE IS

3611
02:01:15,480 --> 02:01:17,720
QUITE GOOD FOR WHATEVER REASON

3612
02:01:17,720 --> 02:01:21,120
AT MAINTAINING PEOPLE'S WEIGHT

3613
02:01:21,120 --> 02:01:22,120
LOSS.

3614
02:01:22,120 --> 02:01:23,840
WHEREAS THE ENERGY INTAKE

3615
02:01:23,840 --> 02:01:25,160
DOESN'T REALLY MAKE TOO MUCH OF

3616
02:01:25,160 --> 02:01:29,720
AN EFFECT, AND PERHAPS THAT'S --

3617
02:01:29,720 --> 02:01:30,880
ONE WAY THAT YOU COULD THINK

3618
02:01:30,880 --> 02:01:32,600
ABOUT THAT IS THAT THE FEEDBACK

3619
02:01:32,600 --> 02:01:34,160
CONTROL CIRCUIT THAT'S GOVERNING

3620
02:01:34,160 --> 02:01:35,240
APPETITE, WHILE YOU'RE BASICALLY

3621
02:01:35,240 --> 02:01:36,240
ALLOWING PEOPLE TO EAT A LITTLE

3622
02:01:36,240 --> 02:01:37,800
BIT MORE FOOD IF THEY'RE

3623
02:01:37,800 --> 02:01:39,520
EXERCISING AND SO THE FEEDBACK

3624
02:01:39,520 --> 02:01:41,160
CONTROL STRENGTH ON THE APPETITE

3625
02:01:41,160 --> 02:01:45,600
SIDE IS NOT QUITE AS HIGH, IF

3626
02:01:45,600 --> 02:01:46,200
YOU'RE EXERCISING.

3627
02:01:46,200 --> 02:01:48,200
AT LEAST THAT'S ONE THEORETICAL

3628
02:01:48,200 --> 02:01:49,360
WAY TO LOOK AT IT AND YOU COULD

3629
02:01:49,360 --> 02:01:51,080
DESIGN STUDIES TO TEST THAT

3630
02:01:51,080 --> 02:01:51,680
HYPOTHESIS.

3631
02:01:51,680 --> 02:01:53,760
BUT IT'S VERY INTERESTING TO ME

3632
02:01:53,760 --> 02:01:56,800
THAT THE EFFECTS OF EXERCISE ARE

3633
02:01:56,800 --> 02:01:59,760
MINIMAL FOR WEIGHT LOSS DURING

3634
02:01:59,760 --> 02:02:01,240
THE ACTIVE WEIGHT LOSS PHASE AND

3635
02:02:01,240 --> 02:02:02,160
THEY SEEM TO REVEAL THEMSELVES

3636
02:02:02,160 --> 02:02:03,360
IN THE WEIGHT LOSS MAINTENANCE

3637
02:02:03,360 --> 02:02:04,640
PHASE AS BEING QUITE AN

3638
02:02:04,640 --> 02:02:06,880
EFFECTIVE TOOL TO KEEP THE

3639
02:02:06,880 --> 02:02:08,240
WEIGHT OFF IF YOU CAN MAINTAIN A

3640
02:02:08,240 --> 02:02:10,720
HIGHER LEVEL OF EXERCISE.

3641
02:02:10,720 --> 02:02:14,320
>>I WOULD SAY WE WERE
VERY

3642
02:02:14,320 --> 02:02:15,600
EXCITED AT THE BEGINNING TO

3643
02:02:15,600 --> 02:02:16,440
THINK THAT EXERCISE COULD

3644
02:02:16,440 --> 02:02:18,040
INCREASE BROWN ADIPOSE TISSUE

3645
02:02:18,040 --> 02:02:19,360
ACTIVITY AND THEY WOULD WORK

3646
02:02:19,360 --> 02:02:20,280
TOGETHER, BECAUSE YOU'RE TALKING

3647
02:02:20,280 --> 02:02:23,000
ABOUT AN ADRENERGIC STIMULUS AND

3648
02:02:23,000 --> 02:02:26,000
SO YOU HAVE EPINEPHRINE OR

3649
02:02:26,000 --> 02:02:27,040
ADRENALINE, NOR OWE ADRENALINE

3650
02:02:27,040 --> 02:02:28,320
IN THE BLOOD, BUT THE LEVELS

3651
02:02:28,320 --> 02:02:29,480
THAT ONE FINDS IN EXERCISE ARE

3652
02:02:29,480 --> 02:02:30,680
NOT NEARLY ENOUGH TO ACTIVATE

3653
02:02:30,680 --> 02:02:32,640
THE BROWN ADIPOSE TISSUE, AND AT

3654
02:02:32,640 --> 02:02:34,040
ONE LEVEL -- SO NOTHING HAS BEEN

3655
02:02:34,040 --> 02:02:35,760
SHOWN TO REALLY BE EFFECTIVE IN

3656
02:02:35,760 --> 02:02:37,080
THAT WAY AND IT POSSIBLE BECAUSE

3657
02:02:37,080 --> 02:02:39,080
WHEN YOU EXERCISE SUFFICIENTLY,

3658
02:02:39,080 --> 02:02:40,160
THE CORE GETS WARM AND IT SHUTS

3659
02:02:40,160 --> 02:02:42,520
DOWN THE BROWN ADIPOSE TISSUE.

3660
02:02:42,520 --> 02:02:47,200
AND SO, THEREFORE, EXERCISE I'S

3661
02:02:47,200 --> 02:02:48,320
BENEFIT IN TERMS OF BROWN

3662
02:02:48,320 --> 02:02:49,640
ADIPOSE TISSUE FUNCTION WOULD BE

3663
02:02:49,640 --> 02:02:50,040
MORE INDIRECT.

3664
02:02:50,040 --> 02:02:52,200
IT MIGHT IMPROVE INSULIN

3665
02:02:52,200 --> 02:02:54,720
SENSITIVITY, IT MIGHT IMPROVE

3666
02:02:54,720 --> 02:02:56,600
CATECHOLAMINE SIGNALING,

3667
02:02:56,600 --> 02:02:57,840
SIGNALING NOREPINEPHRINE AND

3668
02:02:57,840 --> 02:02:58,800
EPINEPHRINE SO THAT THEY WORK

3669
02:02:58,800 --> 02:02:59,000
BETTER.

3670
02:02:59,000 --> 02:03:00,480
SO IT'S NOT GOING TO BE

3671
02:03:00,480 --> 02:03:01,400
SOMETHING THAT CAUSES A

3672
02:03:01,400 --> 02:03:02,720
SPROUTING OF BROWN FAT, BUT IT

3673
02:03:02,720 --> 02:03:04,120
MIGHT MAKE IT WORK BETTER, KIND

3674
02:03:04,120 --> 02:03:06,640
OF LIKE WHAT KEVIN WAS

3675
02:03:06,640 --> 02:03:08,640
DESCRIBING, THAT IT'S NOT REALLY

3676
02:03:08,640 --> 02:03:10,600
FOR WEIGHT LOSS THROUGH ENERGY

3677
02:03:10,600 --> 02:03:12,240
EXPENDITURE DIRECTLY, IT'S MORE

3678
02:03:12,240 --> 02:03:13,920
FOR OTHER EFFECTS.

3679
02:03:13,920 --> 02:03:17,080
>>SO, YO UNFORTUNATELY WE
HAVEO

3680
02:03:17,080 --> 02:03:18,720
END, BUT WE HAVE LOTS MORE

3681
02:03:18,720 --> 02:03:19,960
QUESTIONS.

3682
02:03:19,960 --> 02:03:21,880
AND THERE'S ONE IN PARTICULAR

3683
02:03:21,880 --> 02:03:25,040
WHICH MAYBE IS A SUITABLE ONE TO

3684
02:03:25,040 --> 02:03:26,720
CONCLUDE, WE'VE GOTTEN SEVERAL

3685
02:03:26,720 --> 02:03:31,000
INQUIRIES ABOUT THIS.

3686
02:03:31,000 --> 02:03:32,960
I GUESS THE QUESTION IS, WAS

3687
02:03:32,960 --> 02:03:37,000
MICHAEL POLLAN RIGHT SUGGESTING

3688
02:03:37,000 --> 02:03:39,960
THAT WHEN PEOPLE GO TO A

3689
02:03:39,960 --> 02:03:42,440
SUPERMARKET, THEY SHOULD STAY IN

3690
02:03:42,440 --> 02:03:44,560
THE SECTION WHERE THE FRESH

3691
02:03:44,560 --> 02:03:51,000
PRODUCE IS AND STAY AWAY FROM

3692
02:03:51,000 --> 02:03:55,400
THE FROZEN, THE PROCESSED, AND

3693
02:03:55,400 --> 02:03:57,720
EVERYTHING, AND THEY'LL REMAIN

3694
02:03:57,720 --> 02:04:00,640
HEALTHIER?

3695
02:04:00,640 --> 02:04:03,400
IS THAT A REASONABLE SUGGESTION

3696
02:04:03,400 --> 02:04:05,480
REGARDING ALL THESE VARIOUS

3697
02:04:05,480 --> 02:04:07,800
DIETS AND UNCERTAINTY ABOUT

3698
02:04:07,800 --> 02:04:09,360
THEIR EFFECTIVENESS IN

3699
02:04:09,360 --> 02:04:11,280
EVERYBODY?

3700
02:04:11,280 --> 02:04:17,120
OR IS THAT JUST AN INTERESTING

3701
02:04:17,120 --> 02:04:19,040
IDEA?

3702
02:04:19,040 --> 02:04:20,400
I MEAN, CERTAINLY AS PUBLIC

3703
02:04:20,400 --> 02:04:21,400
POLICY, IT'S PROBABLY NOT A

3704
02:04:21,400 --> 02:04:23,480
GREAT IDEA BECAUSE NOT EVERYONE

3705
02:04:23,480 --> 02:04:26,120
HAS THE MONEY AND THE TIME, THE

3706
02:04:26,120 --> 02:04:28,280
EQUIPMENT, AND THE SKILL AND THE

3707
02:04:28,280 --> 02:04:30,320
STORAGE SPACE REQUIRED TO

3708
02:04:30,320 --> 02:04:32,000
PREPARE MEALS IN THAT WAY.

3709
02:04:32,000 --> 02:04:33,680
IT'S ONLY THE VERY PRIVILEGED

3710
02:04:33,680 --> 02:04:36,760
FEW WHO HAVE THAT.

3711
02:04:36,760 --> 02:04:39,240
SO IF WE COULD MAGICALLY MAKE

3712
02:04:39,240 --> 02:04:39,840
THE COUNTRY HAVE -- EVERYBODY

3713
02:04:39,840 --> 02:04:41,040
HAVE ALL OF THOSE THINGS, THEN I

3714
02:04:41,040 --> 02:04:42,440
THINK THAT WOULD BE REALLY

3715
02:04:42,440 --> 02:04:43,320
EFFECTIVE POLICY ADVICE.

3716
02:04:43,320 --> 02:04:45,200
BUT WE DON'T.

3717
02:04:45,200 --> 02:04:46,400
AND SO I THINK THE QUESTION IS,

3718
02:04:46,400 --> 02:04:50,240
HOW DO WE MAKE FOODS THAT ARE

3719
02:04:50,240 --> 02:04:51,600
ACTUALLY -- PROMOTE HEALTH AND

3720
02:04:51,600 --> 02:04:53,080
PREVENT CHRONIC DIET-RELATED

3721
02:04:53,080 --> 02:04:55,120
DISEASES, HOW DO WE MAKE THAT

3722
02:04:55,120 --> 02:04:56,080
MORE AVAILABLE TO THE REST OF

3723
02:04:56,080 --> 02:04:57,320
THE COUNTRY WHO DOESN'T HAVE

3724
02:04:57,320 --> 02:04:59,920
THAT KIND OF PRIVILEGE.

3725
02:04:59,920 --> 02:05:01,440
>>AARON, YOU WANT THE
LAST

3726
02:05:01,440 --> 02:05:03,200
WORD?

3727
02:05:03,200 --> 02:05:06,720
>>MY LAST WORD IS THAT I
AGREE

3728
02:05:06,720 --> 02:05:09,040
WITH DR. HALL'S DESCRIPTION OF

3729
02:05:09,040 --> 02:05:09,680
THE SITUATION.

3730
02:05:09,680 --> 02:05:13,040
I THINK THAT BEYOND THAT, I HOPE

3731
02:05:13,040 --> 02:05:15,360
PEOPLE ARE LISTENING, RECOGNIZE

3732
02:05:15,360 --> 02:05:17,800
JUST HOW FASCINATING THIS FIELD

3733
02:05:17,800 --> 02:05:19,000
IS, HOW MUCH WE'VE LEARNED, HOW

3734
02:05:19,000 --> 02:05:21,040
MUCH MORE WE STILL HAVE TO LEARN

3735
02:05:21,040 --> 02:05:21,840
AND THAT PEOPLE SHOULD SUPPORT

3736
02:05:21,840 --> 02:05:25,240
THE RESEARCH EFFORTS THROUGH ANY

3737
02:05:25,240 --> 02:05:27,240
WAY POSSIBLE BECAUSE WE'VE GOT

3738
02:05:27,240 --> 02:05:29,160
REALLY TALENTED PEOPLE WHO ARE

3739
02:05:29,160 --> 02:05:31,120
TRYING TO MAKE A DIFFERENCE.

3740
02:05:31,120 --> 02:05:34,120
>>SO ON THAT NOTE, WHICH
I'M

3741
02:05:34,120 --> 02:05:36,120
SURE EVERYONE LISTENING WOULD

3742
02:05:36,120 --> 02:05:38,160
HARDLY AGREE, I'M SURE THERE ARE

3743
02:05:38,160 --> 02:05:40,280
HUNDREDS IF NOT MAYBE SEVERAL

3744
02:05:40,280 --> 02:05:41,200
THOUSAND PEOPLE WATCHING ALL

3745
02:05:41,200 --> 02:05:43,720
THIS FROM AROUND THE WORLD, SO

3746
02:05:43,720 --> 02:05:46,400
ON THEIR BEHALF, AND CERTAINLY

3747
02:05:46,400 --> 02:05:49,160
MY OWN, I WANT TO THANK YOU BOTH

3748
02:05:49,160 --> 02:05:51,040
VERY MUCH FOR AN EXTREMELY

3749
02:05:51,040 --> 02:05:52,400
INFORMATIVE, EXCITING

3750
02:05:52,400 --> 02:05:54,240
PRESENTATION, GIVING US MUCH TO

3751
02:05:54,240 --> 02:05:57,880
THINK ABOUT, AND INDICATING THE

3752
02:05:57,880 --> 02:05:59,840
IMPORTANCE OF BUILDING BRIDGES

3753
02:05:59,840 --> 02:06:01,640
IN ALL DIFFERENT DIRECTIONS.

3754
02:06:01,640 --> 02:06:05,360
SO THANK YOU AGAIN, AND WE WILL

3755
02:06:05,360 --> 02:06:06,200
END THE SESSION.

3756
02:06:06,200 --> 00:00:00,000
THANK YOU.