ob it e id i ?obesity epidemic?inbios21/pdf/fall2007/schneider...¾diet drinks make you hungry!...

Ob it E id i ?Ob it E id i ?Obesity Epidemic?Obesity Epidemic?

Detail of chromosome 15From the obesity map database

Bacchus, Peter Paul Reubens, 1638

Recent Increases in ObesityRecent Increases in Obesity1985: <15% obeseobese2000: >30% obeseIs obesity a disease?

-not all obese people have poor health

What’s causing this unusualIncrease in obesity?

Our genes?-Our genes?-Environment?

fast foodssedentary

lifestyle-Dieting, especially low fat diets-Food choices that blind our natural ability to monitor our food intake

Ob it E i tOb it E i tObesity: EnvironmentObesity: EnvironmentIt’s those damn corporationsIt’s those damn corporationsIt s those damn corporationsIt s those damn corporations

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again shall be kingagain shall be kingg gg g

Obesity: EnvironmentObesity: EnvironmentObesity: EnvironmentObesity: EnvironmentSedentary LifestyleSedentary LifestyleSedentary LifestyleSedentary Lifestyle

Obesity: RidiculousnessRidiculousness

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Obesity: EnvironmentObesity: EnvironmentObesity: EnvironmentObesity: EnvironmentDiets too high in fat?Diets too high in fat?

T h t d d i ?T h t d d i ?QuickTime™ and a

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are needed to see this picture.Too much meat and dairy?Too much meat and dairy?Diets too high in Diets too high in carbohydrates?carbohydrates?

are needed to see this picture. are needed to see this picture.

carbohydrates?carbohydrates?Too much sugar Too much sugar Refined flourRefined flourSoft drinksSoft drinks

Diet drinks make you hungry!Diet drinks make you hungry!Let’s poke








Let s pokecarbohydratesin the eyeball

D BTIFF (Uncompressed) decompressorare needed to see this picture. Dave Barry

Avoiding Obesity: It’s all aboutAvoiding Obesity: It s all about self-discipline, will power,

determinationdeterminationGood Mouse

Bad Mouse

Recent Increases in ObesityRecent Increases in Obesity

1985: <15%1985: <15% obese

2000: >30% obese

Sexually Dimorphic Mammalian SpeciesSexually Dimorphic Mammalian Species

Humans are DimorphicHumans are DimorphicHumans are DimorphicHumans are DimorphicMales Males

Taller, heavierTaller, heavierBroader shoulderBroader shoulderSmaller hips, buttocksSmaller hips, buttocksS ll b tS ll b tSmaller breastsSmaller breastsMore facial hairMore facial hairDeeper voiceDeeper voiceLarger phallusLarger phallusLarger phallusLarger phallusLess stamina due to lower Less stamina due to lower subcutaneous fatsubcutaneous fatMore heart disease due to More heart disease due to tendency to gain abdominal tendency to gain abdominal body fatbody fat

Sexual Dimorphism in Body Fat Sexual Dimorphism in Body Fat Distribution in HumansDistribution in HumansDistribution in HumansDistribution in Humans

Abdominal vs. Subcutaneous FatAbdominal vs. Subcutaneous FatResults in Apple vs. Pear ShapeResults in Apple vs. Pear Shape

Diabetes and Heart Risks if. .Diabetes and Heart Risks if. .

≥≥ 150 mg/dL150 mg/dLTriglyceridesTriglycerides ≥≥ 150 mg/dL150 mg/dL

“Good Cholesterol” = High“Good Cholesterol” = High--Density Density Lipoprotein CholesterolLipoprotein Cholesterol

MenMen< 40 mg/dL< 40 mg/dL

WomenWomen < 50 mg/dL< 50 mg/dL

NCEP Expert Panel. JAMA. 2001;285:2486-2497.

Plasma Triglycerides and HDLPlasma Triglycerides and HDL--CCin Lean Men and Women and in Obese Subjectsin Lean Men and Women and in Obese Subjectsin Lean Men and Women and in Obese Subjects in Lean Men and Women and in Obese Subjects

with High or Low Visceral Adipose Tissue (AT)with High or Low Visceral Adipose Tissue (AT)

2 83.5 1.50

1

0 71.42.12.8

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1.25

1.00

0 75

1

1

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Lean Men Visceral AT Area

Obese Men

Low High

este

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Lean Men Visceral AT Area

Obese Men

Low High

0.750.00

2.12.83.5

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Lean Women

Low High Lean Women

Low High

1.00

0.750.00

Despres JP, Krauss RM. Handbook of Obesity. 1998;651-675.

Women Visceral AT AreaObese Women

Women Visceral AT AreaObese Women

Traits Associated with WTH in WomenTraits Associated with WTH in Women

TraitTrait WTH HighWTH High WHT LowWHT Low RefRef..P b t tP b t t l tl t ll 11Puberty onsetPuberty onset latelate earlyearly 11TestosteroneTestosterone highhigh lowlow 22TriglyceridesTriglycerides highhigh lowlow 1,31,3Insulin resistanceInsulin resistance highhigh lowlow 1,41,4Risk for Type IIRisk for Type IIdiabetesdiabetes highhigh modmod--lowlow 1,51,5

For gallbladderFor gallbladderdiseasedisease highhigh modmod--lowlow 66

Risk for cancerRisk for cancer(ovar.,breast, uterine)(ovar.,breast, uterine) highhigh modmod--lowlow 7,87,8Hypertension, strokeHypertension, stroke

heart disease,heart disease,mortalitymortality highhigh modmod--lowlow 3,5,93,5,9

Adaptive significance Adaptive significance of of

S l Di hi iS l Di hi iSexual Dimorphism in Sexual Dimorphism in Body Fat DistributionBody Fat DistributionBody Fat DistributionBody Fat Distribution

related to female lactationrelated to female lactation(fat is stored in the hips, thighs,(fat is stored in the hips, thighs,(fat is stored in the hips, thighs, (fat is stored in the hips, thighs, buttocks for use in making milk buttocks for use in making milk

during lactation)during lactation)during lactation)during lactation)

An enzyme active in weight gain is An enzyme active in weight gain is high in thighs prior to lactationhigh in thighs prior to lactationhigh in thighs prior to lactation.high in thighs prior to lactation.

High LPL = gaining fatHigh LPL = gaining fatLow LPL = losing fatLow LPL = losing fatLow LPL losing fatLow LPL losing fat

30

ivity Femoral

AbdominalGaining in thighs

20

ipas

e A

ct

AbdominalLosing in thighs

10

opro

tein

L

0Menstruating Pregnant Lactating

Lipo

Menstruating Pregnant Lactating

Rebuffe’-Scrive et al., 1974

Nonabdominal Nonabdominal fatfatiti l fiti l fcritical for critical for

reproductionreproductionreproductionreproductionAnd it’s not unhealthy!And it’s not unhealthy!And it’s not unhealthy!And it’s not unhealthy!

It might even be “protective”It might even be “protective”g pg pagainst diabetes and heart against diabetes and heart

diseasediseasediseasedisease

Regardless of female body Regardless of female body i hti htweightweight

(whether the females are very fat, very (whether the females are very fat, very ( y , y( y , ylean or in between)lean or in between)

A large body of data supports the A large body of data supports the notion that males of North or South notion that males of North or South American or Europe strongly prefer American or Europe strongly prefer

a LOW W.T.H. ratioa LOW W.T.H. ratio

Health Risks and ObesityHealth Risks and ObesityHealth Risks and ObesityHealth Risks and Obesity

Abdominal (apple) Subcutaneous (pear)

Insulin resistance No known health risks

HyperinsulinemiaHypercholesterolemiaLow HDL cholesterol Diabetes mellitus Coronary artery disease HypertensionHypertension Stroke

Science sides with Sir MixAlotScience sides with Sir MixAlot

Wh t ki d f id i hWh t ki d f id i hWhat kind of epidemic has so What kind of epidemic has so many healthy people?many healthy people?y y p py y p p

Marilyn MonroeBMI = overweight to obese

obeseBadCholesterol

lean low highWHT

LeptinLeptinLeptinLeptin

Significance of LeptinSignificance of LeptinSignificance of LeptinSignificance of Leptin

It appears that body weight is regulatedIt appears that body weight is regulatedIt appears that body weight is regulatedIt appears that body weight is regulated

By a “lipostat”By a “lipostat”

Leptin commonly thought to be the Leptin commonly thought to be the lipostatic signallipostatic signallipostatic signallipostatic signal

It is still hoped by many that ourIt is still hoped by many that ourIt is still hoped by many that our It is still hoped by many that our knowledge of leptin will lead to a cure for knowledge of leptin will lead to a cure for obesityobesityobesityobesity

The SeductiveThe SeductiveThe Seductive The Seductive Lipostatic HypothesisLipostatic Hypothesis

Food Intake

Mystery SignalMystery Signal

Body FATBody FAT

It’ OK t l ithIt’ OK t l ithIt’s OK to sleep with a It’s OK to sleep with a hypothesishypothesishypothesis.hypothesis.

You should never marry one.You should never marry one.

HistoryHistoryHistoryHistoryEarly evidence (1970s) for a lipostat came from mutant Early evidence (1970s) for a lipostat came from mutant y ( ) py ( ) pmice that were obesemice that were obeseOb/ob mouseOb/ob mouseDb/db mouseDb/db mouse

Mutation in a single gene on an autosomeMutation in a single gene on an autosomeObese (more than 30% heavier than wild type)Obese (more than 30% heavier than wild type)Obese (more than 30% heavier than wild type)Obese (more than 30% heavier than wild type)Hyperphagic (ate significantly more than wild typeHyperphagic (ate significantly more than wild typeDiabetic (hyperglycemic)Diabetic (hyperglycemic)Infertile (does not undergo puberty does not mate or haveInfertile (does not undergo puberty does not mate or haveInfertile (does not undergo puberty, does not mate or have Infertile (does not undergo puberty, does not mate or have estrous cycles or spermatogenesis, decreases gonadal steroids)estrous cycles or spermatogenesis, decreases gonadal steroids)

ParabiosisParabiosis

An obese mouse (ob/ob) is sharing its circulation An obese mouse (ob/ob) is sharing its circulation ( ) g( ) gwith a lean wild type mousewith a lean wild type mouse

How would you explain these results?How would you explain these results?

ob/ob ob/ob -- +/+mouse: ob/ob lost weight+/+mouse: ob/ob lost weightdb/dbdb/db / db/db b / t d ti d l t i ht/ db/db b / t d ti d l t i htdb/dbdb/db-- +/+ :db/db obese, +/+ stopped eating and lost weight+/+ :db/db obese, +/+ stopped eating and lost weightob/ob ob/ob --db/db: ob/ob stopped eating and lost weight, whereas the db/db: ob/ob stopped eating and lost weight, whereas the db/db unaffecteddb/db unaffectedAn additional experiment showed that when one of a pair of +/+An additional experiment showed that when one of a pair of +/+An additional experiment showed that when one of a pair of +/+ An additional experiment showed that when one of a pair of +/+ parabiotic mice was overfed, its "twin" lost weight.parabiotic mice was overfed, its "twin" lost weight.

Conclusion?Conclusion?

Conclusion of Parabiosis Conclusion of Parabiosis ExperimentExperiment

The ob/ob has a mutation in the gene thatThe ob/ob has a mutation in the gene thatThe ob/ob has a mutation in the gene that The ob/ob has a mutation in the gene that codes for a circulating factor that stops the codes for a circulating factor that stops the rat from eatingrat from eatingrat from eating.rat from eating.The db/db has a mutation in the gene that The db/db has a mutation in the gene that codes for the receptor for this factorcodes for the receptor for this factorcodes for the receptor for this factorcodes for the receptor for this factor

Conclusions of Parabiosis Conclusions of Parabiosis ExperimentExperiment

Ob/ob lacks a factor that stops eatingOb/ob lacks a factor that stops eatingThe db/db lacks the receptor for that factorThe db/db lacks the receptor for that factorThe db/db lacks the receptor for that factorThe db/db lacks the receptor for that factor

Leptin (Ob protein)Leptin (Ob protein)Leptin (Ob protein)Leptin (Ob protein)Cloned by J. Friedman’s lab in 1994 (Zhang et al., 1995)Cloned by J. Friedman’s lab in 1994 (Zhang et al., 1995)

Adipocyte protein secretedAdipocyte protein secretedin proportion to body fat contentin proportion to body fat contentin response to influx of fuels into adipocytes (in response to influx of fuels into adipocytes (

Plasma concentrationsPlasma concentrationshigh in fat, fed animalshigh in fat, fed animalslow in lean or fasted animalslow in lean or fasted animals

Peripheral and central treatment decreases food intake (FI) Peripheral and central treatment decreases food intake (FI) and body weight (BW) in many different speciesand body weight (BW) in many different species

Ob/ob (leptin decreases food intake and bw)Ob/ob (leptin decreases food intake and bw)Db/db (leptin treatment has no effect)Db/db (leptin treatment has no effect)Wild type mouse (leptin decrease FI and BW)Wild type mouse (leptin decrease FI and BW)Rats Rats HamstersHamstersMonkeysMonkeys

So Is leptin the cure for So Is leptin the cure for obesity?obesity?

Percentage of people who are obese because they Percentage of people who are obese because they g p p yg p p yhave a mutation in the gene for leptin = miniscule have a mutation in the gene for leptin = miniscule (only a few people in the world have this mutation)(only a few people in the world have this mutation)Clinical trials a failureClinical trials a failureClinical trials a failureClinical trials a failure

gave daily leptin injections to obese patients. gave daily leptin injections to obese patients. Only a third of the patients lost weight. Only a third of the patients lost weight. Some patients dropped out of the study finding theSome patients dropped out of the study finding theSome patients dropped out of the study finding the Some patients dropped out of the study finding the injections irritatinginjections irritatingSome reported decrdased appetite at first, and increased Some reported decrdased appetite at first, and increased appetite after continued use (they developed leptin appetite after continued use (they developed leptin pp ( y p ppp ( y p presistance).resistance).The people gained back the weight they had lost when the The people gained back the weight they had lost when the leptin injections ceased.leptin injections ceased.

Why is Leptin Not The Miracle Cure for Why is Leptin Not The Miracle Cure for Obestiy?Obestiy?Obestiy?Obestiy?

In addtion to leptin, there are In addtion to leptin, there are manymanyhormones and neuropeptides thathormones and neuropeptides thathormones and neuropeptides that hormones and neuropeptides that influence appetite and obesityinfluence appetite and obesity

Giving leptin alone does not curtail Giving leptin alone does not curtail obesityobesityobesityobesity

Obese people have higher leptinObese people have higher leptinObese people have higher leptin Obese people have higher leptin than normal weight peoplethan normal weight people

Some Factors Involved in Energy BalanceSome Factors Involved in Energy BalanceO i ti l S tO i ti l S tOrganizational SystemOrganizational System

Metabolic Stimuliglucose oxidationglucose oxidationffa oxidationketone body formation, oxidationinflux of fuels into adipocytes, muscles, liver, etc.lipolysisp y

Hormonesinsulinglucagonleptinpglucocorticoids (cortisol, corticosterone)ghrelingrowth hormonecholecystokinin (gut peptide)

NeuropeptidesNPYAgRPOrexinCARTa-MSH

RED = INHIBITORYRED = INHIBITORYGREEN STIMULATORYGREEN STIMULATORYGREEN = STIMULATORYGREEN = STIMULATORY

Leptin Insulin GhrelinLeptin Insulin Ghrelin

NPY/AGRP POMC (NPY/AGRP POMC (ααMSH)MSH)(( ))

Increases appetite Decreases appetiteappetite

ARC PVN


are needed to see this picture.LEPTININSULIN

Leptin Re-wires the NPY and POMC CircuitryLeptin Re-wires the NPY and POMC Circuitry

Wildtype mice tend to have more excitatory Wildtype mice tend to have more excitatory synapses in the leptinsynapses in the leptin toto POMC circuit and morePOMC circuit and moresynapses in the leptinsynapses in the leptin--toto--POMC circuit, and more POMC circuit, and more inhibitory synapses in the leptininhibitory synapses in the leptin--toto--NPY circuitNPY circuit



Ob/ob mice tend to have more excitatory synapses in Ob/ob mice tend to have more excitatory synapses in the leptinthe leptin--toto--NPY circuit and more inhibitory synapses NPY circuit and more inhibitory synapses pp y y py y pin the leptinin the leptin--toto--POMC circuitPOMC circuit

Increase Food IntakeIncrease Food IntakeIncrease Food IntakeIncrease Food Intake

Orexin (lateral hypothalamus)Orexin (lateral hypothalamus)NPY (arcuate and PVN)NPY (arcuate and PVN)NPY (arcuate and PVN)NPY (arcuate and PVN)AgRP (arcuate and PVN)AgRP (arcuate and PVN)MCH (l t l h th l )MCH (l t l h th l )MCH (lateral hypothalamus)MCH (lateral hypothalamus)

Decrease Food IntakeDecrease Food IntakeDecrease Food IntakeDecrease Food Intake

POMC (POMC (ααMSH) (arcuate and MSH) (arcuate and PVN)PVN)PVN)PVN)CART (arcuate nucleus)CART (arcuate nucleus)CRH (PVN)CRH (PVN)

Current ResearchCurrent ResearchCurrent ResearchCurrent ResearchAny particular obese individual might have mutations or Any particular obese individual might have mutations or variations at these obesityvariations at these obesity related locirelated locivariations at these obesityvariations at these obesity--related locirelated lociYou cannot assume any one obese person is just lazyYou cannot assume any one obese person is just lazyMany genes, peptides and neurocircuits involvedMany genes, peptides and neurocircuits involvedRedundancy in the systemRedundancy in the systemRedundancy in the systemRedundancy in the systemA drug that influences one of these peptides can be overridden A drug that influences one of these peptides can be overridden by the othersby the othersAs soon as you stop taking the “antiobesity” drug you gain allAs soon as you stop taking the “antiobesity” drug you gain allAs soon as you stop taking the antiobesity drug, you gain all As soon as you stop taking the antiobesity drug, you gain all the weight backthe weight back

Single gene approach unlikely to solve the obesitySingle gene approach unlikely to solve the obesitySingle gene approach unlikely to solve the obesity Single gene approach unlikely to solve the obesity problem.problem.

A Pause That Refreshes

Dieting Dieting Doesn’t WorkDoesn’t Work

Dieting is a signal to the brain to Dieting is a signal to the brain to become better at become better at storingstoring fatfatgg

Energy BalanceEnergy BalancegygyIntakeIntake

Motivational (appetite)Motivational (appetite)( pp )( pp )ConsumptionConsumption

StorageStorageGlycogen in muscle and liverGlycogen in muscle and liverGlycogen in muscle and liverGlycogen in muscle and liverLipid in adipose tissue and other tissuesLipid in adipose tissue and other tissuesAmino acids in muscle and bone (used with glycerol to make new Amino acids in muscle and bone (used with glycerol to make new glucose)glucose)g )g )

ExpenditureExpenditureRestingRestingThermogenesisThermogenesisThermogenesisThermogenesisReproductionReproductionImmune functionImmune functionOth ll l ( it i i i di tiOth ll l ( it i i i di tiOther cellular processes (mitosis, miosis, digestion, Other cellular processes (mitosis, miosis, digestion, metabolism, cell repair)metabolism, cell repair)

Energy BalanceEnergy Balance--- +

Energy BalanceEnergy BalanceNo Free RidesNo Free Rides



IntakeIntakeStorageStoragegg

Glycogen Glycogen in muscle and liverin muscle and liverLipidsLipids in adipose tissue and other tissuesin adipose tissue and other tissuesProteinProtein (Amino acids )in muscle and bone (used with glycerol to (Amino acids )in muscle and bone (used with glycerol to ( ) ( g y( ) ( g ymake new glucose)make new glucose)

ExpenditureExpenditureResting (Basal Metabolic Rate)Resting (Basal Metabolic Rate)Resting (Basal Metabolic Rate)Resting (Basal Metabolic Rate)ThermogenesisThermogenesisReproduction, Immune functionReproduction, Immune function

Restricting Food IntakeRestricting Food IntakeD E E ditD E E ditDecreases Energy ExpenditureDecreases Energy Expenditure

1200

1000

1200

600

800 Ate Adlibitum75%Restricted

200

400

Restricted50%Restricted

0

200

1st Qtr

E ti R iEating Regimen

Rebound results from increased appetite Rebound results from increased appetite l d ith d d ditl d ith d d ditcoupled with decreased expenditurecoupled with decreased expenditure

Dieting Makes you FatDieting Makes you FatDieting Makes you FatDieting Makes you Fateventuallyeventually

I’m sorry LouisI’m sorry LouisI’m sorry, LouisI’m sorry, Louis

Fat doesn’t make you Fat doesn’t make you f t!f t!fat!fat!

Diet low in simple Diet low in simple bbcarbscarbs

are more satisfyingare more satisfyingare more satisfyingare more satisfyingYou feel less hungryYou feel less hungry

You eat lessYou eat lessYou eat lessYou eat less

Good FatsGood FatsGood FatsGood FatsLinoleic Acid has two double bonds, can be hydrogenated and is a

QuickTime™ and aTIFF (Uncompressed) decompressor can be hydrogenated and is a

Polyunsaturated fat.( p ) p


Its formula isCH3(CH2)4CH=CH2CH=CH(CH2)7COOH





p

Bad FatsBad FatsQuickTime™ and a

TIFF (Uncompressed) decompressorare needed to see this picture.

Water insoluble subatances. They have a relatively large nonpolar hydrocarbon part and a small oxygen

t i i l tcontaining polar part.

Stearic acid has a 17 atom hydrocarbon chain and a carboxylic acid groupcarboxylic acid group.

Its chemical formula is CH3(CH2)16COOH and it is a saturated fat


saturated fat.

( p ) pare needed to see this picture.

Given two meals with Given two meals with the same caloric value, the same caloric value,

th l b di tth l b di tthe low carb diet the low carb diet results inresults inresults inresults in

--Significantly more weight lossSignificantly more weight loss--Happier peopleHappier peopleHappier peopleHappier people

--The weight will be gained back if The weight will be gained back if you go back to eating carbsyou go back to eating carbsyou go back to eating carbsyou go back to eating carbs

Don’t DietDon’t DietDon t DietDon t DietMake permanent changesMake permanent changesp gp g

--no soft drinksno soft drinksMinimize bread and pastaMinimize bread and pasta--Minimize bread and pastaMinimize bread and pasta

--eat carbs like vegetables and fruits eat carbs like vegetables and fruits d b id b iand berriesand berries

Di t D i k M k YDi t D i k M k YDiet Drinks Make You Diet Drinks Make You HungryHungryHungryHungry

Growing up on diet drinksGrowing up on diet drinks--precludes your ability to matchprecludes your ability to matchprecludes your ability to match precludes your ability to match

taste with caloric intaketaste with caloric intake--makes you significantly fattermakes you significantly fatter--makes you significantly fattermakes you significantly fatter

Diet Drinks decrease the ability to gauge Diet Drinks decrease the ability to gauge th l i l f f dth l i l f f dthe caloric value of foodthe caloric value of food

Davidson and SwithersDavidson and SwithersDavidson and Swithers, Davidson and Swithers, International Journal of International Journal of ObesityObesity, 28, 933, 2004., 28, 933, 2004.Rats were trained with a Rats were trained with a

Rats were given sweet flavored premeal that matched their

caloric value (consistent)or did t t h (i i t t)flavored premeal and flavored premeal and

then later tested for their then later tested for their food intakefood intakeC i t t GC i t t G

not match (inconsistent)

20Flavored PremealConsistent Group Consistent Group

received flavors that received flavors that consitently predicted the consitently predicted the calorie contentcalorie content

10

Flavored Premeal

Chow meal

Inconsistent Group Inconsistent Group received flavors that did received flavors that did not have any relation to not have any relation to th i l i lth i l i l

0Consistent Inconsistent

Ctheir caloric valuetheir caloric value Caloric Intake

Good luck thisGood luck thisGood luck this Good luck this weekendweekendweekendweekend

--Don’t dietDon’t diet--Don’t drink soft drinks, especially Don’t drink soft drinks, especially dietdietdietdiet--Eat a balance diet of real foods Eat a balance diet of real foods including polyunsaturated fatincluding polyunsaturated fatincluding polyunsaturated fatincluding polyunsaturated fat--To Sir Mixalot with loveTo Sir Mixalot with love

87!

More ReferencesMore ReferencesMore ReferencesMore References

Taubes Gary What if it’s all been a big fatTaubes Gary What if it’s all been a big fatTaubes, Gary, What if it s all been a big fat Taubes, Gary, What if it s all been a big fat lie? lie? New York TimesNew York Times, Sept. 15, 2002., Sept. 15, 2002.

Pollen, Michael, Unhappy Meals, Pollen, Michael, Unhappy Meals, New New Y k TiY k Ti J 28 2007J 28 2007York TimesYork Times, January 28, 2007., January 28, 2007.

ob it e id i ?obesity epidemic?inbios21/pdf/fall2007/schneider...¾diet drinks make you hungry!...

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