Obesity Exam 2

Bottom Line about Genetics and Intake

Genetics plays a small but significant role in determining human food intake

Mean BMI over the past decade

Has increased

Average Daily Food intake

Is correlated with lean body mass, not fat mass

Do we have a biological mechanism that compensates for energetic errors?

NO

Amphetamines

-- Either decreased intake or increased metabolic rate --Initially marketed to control narcolepsy; discovered as a derivative of ephedrine

Critical components of set-point theory

--Adipose cell: the brain has to find a way to monitor the amount of fat coming from a fat cell-- there needs to be a signal --If you could find the signal you could increase it to make your body think you have more fat than you do

Freud's Theory of Obesity

--Based on inability to progress from anal stage of development

Negative Food Primes

--Blocks the effects of a positive food prime --One is a bathroom scale: stepping on the scale makes you less likely to succumb to positive food primes

Study by Andersson and Larsson

--Brain temperature of goats heated and cooled: if you warm the brain eating stops and thirst increases, if you cool the brain eating begins again until you start warming the brain again --Heating and cooling goat brain controls eating --Proves that warming produces inhibition of appetite --Problems: range of temperatures are un-physiologic because the temperature of the brain stays relatively constant

CCK Conclusions

--CCK probably does reduce feeding --Acts by delaying gastric emptying (total intake goes down) --May work as a safety mechanism to prevent continual gorging --But probably doesn't play a role in meal to meal regulation; not the reason you stop eating after a meal

Can odor increase food intake

--Digestion starts before you get food in your mouth --First phase of digestion: thinking/smelling/discussing food elicits changes in the GI tract so that you prepare for food --Pavlov: dogs smelling food leads to salivation-- this can be conditioned --Explains food habits --Bakery section of Wegmans smells nice because smell makes us want to purchase food

Reducing Fat Cryogenically/Coo Sculpting

--Does not really work --The residual cells increase in their size just like you see after liposuction lipectomies (paradoxical adipose hyperplasia)

Restrictions on amphetamines

--Due to their abuse potential they were restricted to 12 weeks of therapy

Eating in the absence of hunger (EAH) phenotype

--Girls who showed EAH at age 7 showed higher BMI at age 9 --The tendency to eat after a meal wen you are not hungry is higher in obese children; they have a greater response to food in the absence of hunger

Tasting with our ears

--Higher pitched sounds while eating crunchy foods makes you eat more (increases crispness perception) --Sweet solutions rated as more pleasant when consumed with loud noise or music --Alcoholic drinks rated as sweeter with loud music --Pleasantness of coffee or potato chips is increased when you hear congruent sounds --Sea sounds increase pleasantness of seafood

Hedonic Rating

--How sweet something tastes

Erasmus Darwin

--Hunger caused by absence of contractions --1801 (not accurate)

Set Point Theory

--Hypothalamic areas (VMH and LH) in the brain read the amount of body fat you have --They know how much you should have and if the two differ it will modify eating behavior

CCK in Humans

--Infusion of CCK causes reduction in hunger and decrease in intake (but dose was MUCH higher than physiologic) --Lower doses of CCK can cause changes in hunger without causing changes in intake --CCK makes people nauseous; it is hard to tell nausea from a normal satiety mechanism --A decrease in hunger without decrease in intake is not biologically relevant-- many things can affect hunger

Orilistat

--Introduced in 1999 --Inhibits pancreatic lipase; can't break down triglycerides in food or absorb them --Blocks 30% of total fat absorbed --3% weight loss --No evidence of harm

Does low birthweight lead to later obesity

--Most human studies do not find low birthweight causes increased BMI in childhood or adulthood

Quest to Figure Out What Controls Body Weight

--Mouth has some satiety power but not enough to explain it --Hormones release in the stomach but not enough to explain it --Hemofactors like glucose and amino acids are not sufficiently powerful to explain why we are getting fatter

Things that are NOT the cause of eating

--Mouth: taste, smell-- no specific cause of eating --Stomach: interesting things and surgeons take advantage of it but not the natural cause of eating --Glucose: not stimulus for eating or satiety

Gary Taubes: Good Calories, Bad Calories and more

--NYT writer --good writer, bad scientist --writers say the problem is CARBS not calories --Levitsky says this isn't the case

Do we compensate for snacking?

--On days people consume snacks, people consume far more calories over time --Meals are not affected by eating the snack --Snacking simply adds calories; we don't detect that we've added calories --NO

Can chewing gum help you reduce weight

--One study: chewing gum decreases intake of sweet snacks if you chew it before --Another study: chewing gum increases expenditure (can get 50 calorie daily deficit if you chew gum 24/7) --A third study: NO DATA SHOWING WEIGHT CHANGE IN RESPONSE TO GUM CHEWING-- theoretical did not translate to real

Medical Bias

--Only half of the obese suffer from diabetes, hypertension, hyperlipidemia

How much of our satiation feelings are caused by the mouth?

--Oral cavity plays a major role in feeling less hungry --If you consume food orally your hunger rating goes down as you consume --If you put food directly into the stomach your hunger rating doesn't go down as much --If you put food directly into the small intestine, you don't feel any satiety

Obesity Paradox

--Overweight individuals have better prognosis following heart failure than underweight and normal weight people --Study: low fitness individuals have the obesity paradox, high fitness individuals have no obesity paradox because the effect of low body weight increasing the risk of dying doesn't exist if you maintain a high physical fitness --Fitness is protective against dying

Study adding air to decrease energy density

--People consume less of the aerated food --ENERGY DENSITY CONTROLS HOW MUCH WE CONSUME

Other arguments raised in favor of low carb/high protein diet

--People have been reducing their fat intake but are getting fatter anyway --People have been increasing their carbs and getting fatter --BOTH NOT TRUE WHEN YOU LOOK AT DATA --Fat intake is increasing; no calorie regulation --Carb intake is not going up --Protein is constant --NO evidence that fat intake has decreased

Weight loss on a low carb diet study

--People lose weight over time --Many dropped out; lots of people can't stick with this diet --As study length increases weight loss plateaus --If you stay on the diet you will wee 10% weight loss

Correlation in weights between members of the same family

--People tend to marry people of their same BMI --Parent/child correlation is higher than spousal (due to genes) --Sibling correlation is even higher because they share more genes --EVEN THE STRONGEST CORRELATION ONLY ACCOUNTS FOR 10% OF VARIANCE

Activity and BMI

--People with higher levels of exercise (higher METS) have lower BMIs --People with higher BMIs expend fewer calories in physical activity (both in males and females

Physical Activity Decline

--Physical activity energy expenditure has not declined since the 1980s and matches energy expenditures of wild mammals --Examining primitive peoples: their energy expenditure is not significantly different than modern people

Candidates for set-point theory signal

--Progesterone pulses: released in bursts and the brain can sense it --Adipsin: an adipokine produced by adipose cells --Glycerol: a function of the total amount of adipose you have-- injections of glycerol can casue reductions in intake (physiologic)

Johannes Muller

--Proposed that hunger was caused by the absence of satiety signals from the stomach --Based on neuroanatomy

Rate of Eating Phenotype

--Rate of eating is greater in obese children than non-obese --The decrease in rate over a meal is also less

Cafeteria Feeding

--Rats are normally individually fed --Cafeteria Feeding: Rats are fed in large cages and given a variety of high fat and high sugar food and the foods are constantly changed --Rats fed this way had much more weight gain; weight was almost exclusively fat tissue; energy intake was almost double that of control animals --When you stop overfeeding they go down but not back to baseline-- obesity caused by cafeteria feeding --The efficiency is much lower in cafeteria fed animals --Cafeteria fed animals had more brown fat and increased thermic activity of brown fat

Fevers caused by:

--Release of interleukin-1 --TNF (Tumor necrosis factor)

AspireAssist

--Removes food from stomach with a tube before it is absorbed and water is pumped into the stomach --Weight loss seen in a study --Problem: can't keep people in the study

Energy expenditure of more primitive living people is not higher than contemporary people

--Resting accounts for high energy expenditure bursts

Summary on stress in humans

--STRESS IS NOT A MAJOR CONTROL OF INTAKE NOR DOES IT PLAY A ROLE IN OBESITY --Field tests of people in combat show a suppression of intake and a decrease in body weight --chronic stress effects on intake rely on self-reported indices of stress and intake

Study Looking at Identical vs. Fraternal Twins and Eating Behavior Questionnaire

--Satiety Responsiveness: significant difference between monozygotic and dizygotic twins (monozygotic were more correlated) --Enjoyment of food: significant difference between monozygotic and dizygotic twins (monozygotic were more correlated) --magnitude of effect still small --MONOZYGOTIC TWINS BEHAVE MORE SIMILARLY IN ALL PARAMETERS-- suggests genetics plays a role

Behaviorism

--School of obesity where you try to understand people by watching their responses-- only look at things you can measure

Derek Miller

--Series of studies looking at thermogenesis and eating behavior --Overfed young men (made them gain weight) a high or low protein diet --The obese were less sensitive to the thermic effect of food (SDA) than the non-obese; suggested that heat was the difference and determinant of obesity

Drugs and weight gain

--Some drugs cause weight gain as a negative side effect

Rate of stomach emptying

--Streching the stomach is a signal not to eat 1. Viscosity is major determinant of when the stomach opens to the intestines (more viscous things stay in the stomach longer where water is added) 2. Soluble, but not insoluble, fiber increases viscosity

Summary of Stress in Animals

--Stress can increase feeding behavior but is not specific to food --NOT LINKED TO OBESITY

Study on the Freshman 15

--Students who weighed themselves every day gained less weight than those who didn't --When people see their weight go up they know they have to eat less later in the day

Does exercise help lose weight

--Study --Found increase in energy expenditure with exercise --Weight decrease significant in males who exercised --In women the exercise group has no change --Exercise causes weight loss in men; exercise prevents weight gain in women

Movement is the most potent stimulus for the sympathetic nervous system

--Suppresses GI tract --Suppresses food intake --Activates lipolysis: direct stimulation of fat cells with norepinephrine activates hormone sensitive lipase which breaks down triglycerides and releases them into the bloodstream

Not everyone is getting fatter

--The fat are getting fatter

Specific Dynamic Action (SDA also known as thermic effect of food)

--The greater the protein intake the greater the thermic effect of food --you can increase expenditure if people are on a high protein low carb diet --PEOPLE CAN'T STAY ON THIS DIET

Variation in snacks

--The greater the variety of snacks, the more obese you tend to be --We have increased the novel foods produced since 1990-- the increase in new food products can at the same time our BMI began to increase

Studies on Fat content increases

--The majority of studies say that there is no compensation to decreasing fat intake --If you decrease the fat content it reduces intake --Reduced caloric intake when you reduce the fat content

Glenn Gaesser: Big Fat Lies and The Spark

--The problem is not that we're eating too much, the problem us we're moving too little --Exercise physiologists like this idea --Levitsky says is wrong

Fletcherism

--Theory of excessive mastication --If you chew food 100 times before you swallow it you will eat less --Is true, if you chew more you do eat less --Is effective in producing weight loss: you consume fewer calories if you chew more

Problems with Amphetamines

--Tolerance: repeated dose decreases anorectic effect, but not any other effects of amphetamine; characteristic of addictive drugs --Body weight effect is suppressed as long as you take the drug even when intake goes back to normal --Study: weight of animals was reduced to where it would be if they normally took the drug and there was no weight suppressing effect; there is no anorexia if you drop the weight first --The anorexia was related to body weight: the effect of the drug depended on body weight and was not true drug tolerance

Exercise and Genetics

--Twin study: correlation in daily energy expenditure higher in identical twins

2,4- Dinitrophenal

--Uncouples oxidative phosphorylation --Occurs in BAT (Uncoupling protein UCP1, 2) --Increases metabolic rate and you lose lots of weight --Used in the 1930s for weight loss --Banned because it caused cataracts and heart attacks

BMI vs. Number of excessive deaths

--Underweight has increased death rate --Obese has increased death rate --Overweight has decreased death rate (obesity paradox): has caused controversy

People who lose weight have an increased chance of dying early

--Unintentional weight loss leads to increased risk of dying --Intentional weight loss lowers the risk of dying

Sherman Mellinkoff 1956

--Unlike sugar protein is indispensable --After a meal blood amino acid rises --High protein diet inhibits appetite in animals

Problems with VMH as satiety center

--VMH lesion alters many behaviors: activity level, drinking, sexual activity, aggressive behavior --VMH stimulation is aversive: an animal will do anything to make stimulation stop --Intact vagus nerve is needed for obesity (controls GI release of enzymes): if you cut the vagus nerve a lesioned VMH doesn't cause obesity --Lesions cause a hypersensitivity of the beta cells in the pancreas that release insulin: insulin causes animals to get fat (maybe it is this and not the VMH)

VO2 Max (Cost of Exercise) and genetics

--VO2 Max: Energy cost of exercise --Twin Study: Identical twins have highly correlated VO2 max at low exercise; at high exercise there is very little difference between identical and fraternal twin correlations --shows there IS a genetic component but the applications are unclear

Using the Mouth to Control weight

--Various devices exist: chewing device (decrease speed of eating), wiring jaw shut, SmartByte (can only take small bites) --You can't keep it up: after 4 weeks all devices stop being used

The idea that carbohydrates are bad

--Very prevalent in our society --Made popular by Dr. Atkins --NIH says 55% of diet should be carbs; Atkins says 5% should be carbs

Why are we overeating?

--We are eating more food prepared outside of the home, particularly fast foods

Reason we overeat when we eat energy dense foods

--We don't have the physiological mechanisms to detect energy density --We keep volume fairly consistent; if you increase energy density you will overeat

We don't have mechanisms to calorically compensate

--We eat a lot at once and don't eat less later --We can't energetically compensate for eating too much or too little

Age Related weight gain

--We gain weight until middle age (steep curve) --Age is the best scientific predictor if those who will become hypertensive, hyperlipidemic, diabetic

Slowing the development of human adipose cells

--We have 2 chances: childhood and puberty --However, the degree of dietary restriction used in animals would be unethical to use in humans --People are looking at chemical ways to reduce the number of cells --WEIGHT REDUCTION IN CHILDHOOD DOE SNOT WORK

Glucose infusions into small intestines

--We have glucose receptors in our small intestines --Glucose infused directly into the liver leads to small decrease in eating but nowhere near that in the intestine --Infusing glucose directly into the intestine results in a 30% decrease in intake --We don't know why there are glucose receptors in the intestines

Glucostatic Theory of Eating

--We have this monitor between the glucose going in and the glucose going out --When we don't eat there is no glucose coming in and there's low insulin => very little glucose utilization (THAT is why you eat) --After eating a meal there is high glucose, high insulin => lots of glucose in the sensors (satiation)

Evolving Technology

--We have transferred hard labor to robots/machines --Screen-based media use leisure activities has increased --HOWEVER the amount of time spent doing physical activity has remained the same

There are no single function receptors in the body

--We will never find a drug that can affect only energy intake or energy expenditure without affecting other systems

Will exercise offset the decrease in metabolic rate caused by dieting

--Weight loss with just exercise: very low --Weight loss of just diet and weight loss of diet plus exercise are exactly the same; exercise had NO impact on the effects of diet --Exercising is NOT a way to enhance your diet -NO

Adiposity rebound

--When children are young they gain weight very quickly --Between ages 5 and 7 there is minimum weight change: point of adiposity rebound --Then there is weight gain again in adolescence --Early adiposity rebound: much higher fat mass --Late adiposity reboud: much lower fat mass --BMI of young adults with earlier rebound have higher BMI

You eat with other people at restaurants

--When we see other people eat, we eat whether we are hungry or not --People eat faster together --People eat larger portions when together --Comes from ancient behaviors that helped us survive with less food

Daily Energy Intake and Fat

--You have a lower overall intake with a lower fat content in the diet --When you reduce dietary fat people lose weight and sustain weight loss: body weight decreases on low fat diet --NO COMPENSATION: if you reduce the amount of calories in your food you do not eat more to compensate (thus you lose weight)

Does exercise help my diet

--You lose both fat and lean body mass when on a diet-- losing lean mass decreases your expenditure --Causes rapid weight loss early and then you stop losing weight --Metabolic rate is a function of fat free mass (muscle tissue) --METABOLIC ADAPTATION occurs: body adapts to weight loss by decreasing metabolic rate

Vagus Nerve Block (vbloc)

--block with electrical stimulation --Whenever you feel hungry you could push a button and take the hunger away: control group has an increase in weight after the weight loss --With vblock there was weight loss and the regain of weight was slower

Yo-yo effect

--diet for a while and then it fails --lose weight, gain weight, etc. and over time you gain weight (people thought that the dieting caused the weight gain, in reality as we age we gain weight)

Dieting is Ineffective: TRUTH

--dieting doesn't actually lead to weight gain --dieting DOES correlate to mortality but we don't understand the cause: people who have a problem to begin with lose weight causing increased mortality or maybe losing weight itself causes mortality

Homeostatic Eating

--eating as a regulatory mechanism that controls amount of body weight or body fat --Fundamental idea of physiology

Insulin Hypothesis

--high carb diets release insulin and insulin stores fat --Insulin as "hunger hormone" study: you see a reduction in food intake right away followed by an increase --Problem: the amount of glucose needed to trigger eating is almost comatose level (BGL of 20) --NOT SUPPORTED BY DATA --Problem: insulin cannot make you fat, you only get fat if you absorb more calories than you expend-- caloric intake drives it and consuming energy in excess of what you expend increases body fat

Study: Rats on diets with different protein levels

--if you feed an animal a decent amount of protein you get a lot of growth --If you feed the animal a high or low protein diet, body weight is lost --

Do we compensate for reducing lunch?

--if you use a meal replacement instead of a lunch you don't eat significantly more later --NO compensation if you eat a meal replacement --There was weight loss on meal replacement

Study: kcal expenditure after eating

--more heat is blown off on a high protein diet --on a high carb diet you blow off less --THIS IS REAL, YOU DO BLOW OFF EXTRA ENERGY

Hilda Bruch

--psychologist interested in eating disorders

Mellinkoff on Study About A-V Difference and Satiety

--showed glucose as directly related to satiety ratings --Mellinkoff said that they were fed a high carb diet in this study --He re-did the study and gave patients a mixed diet --On a mixed diet, hunger ratings DO NOT correlate with change in blood sugar; it was RANDOM --There was a linear relationship between amino acid concentration in the blood and satiety ratings

Thyroid Powders

--thyroid has metabolic hormones --if you eat animal thyroid glands you lose weight becasue you increase the thyroxine produced by the thyroid gland and metabolic rate increases --Used to treat obesity in the 1920s when society started to want women to be skinny --Toxic in high doses-- deaths occurred

Food Efficiency

--want maximum amount of protein on the animal with minimum amount of food (agriculture) --Normally the efficiency is high (85%) --On a high protein diet efficiency is reduced (50%); they can't convert it to energy so it is probably lost as heat

Why do we have condition-able food aversion

1. As mammals we have to learn what to eat and what not to eat (we aren't born knowing what good food is; kids try to eat everything to figure out what is and isn't food) 2. Sub mammals are programmed to know what to eat 3. We depend (mostly) on learning and conditioned aversion is a kind of learning

Imbalanced diet in the brain

1. Brain detects imbalance of amino acids (brain is very sensitive to these imbalanced diets) 2. Responds to imbalanced diet (high or low) by inhibiting intake 3. Problem with feeding people imbalanced diets: ends in nausea and vomiting

Arguments against an epidemic

1. Epidemic of Obesity is being oversold (weight loss industry makes money) 2. Health risks associated with increasing weight are exaggerated 3. BMI is not a good measure of fatness 4. Dieting is ineffective 5. No evidence that weight loss improves health 6. Still don't know what makes people fat (no good data because we interfere with what people eat every time we study it) 7. Social ideals of body size change over time 8. Exercise is more important than weight loss 9. Not everyone is getting fatter, fat people are getting fatter

Conditioning Food Aversion

1. Give animal a novel food to eat 2. After eating make the animal nauseous 3. Next day give animal choice between 2 foods 4. Animal will avoid "sick" food

Hypothesis as to why low carb diets lead to weight loss

1. Metabolic hypothesis 2. Insulin hypothesis 3.

Unique Features of Food Aversion Learning

1. Must make the animal nauseous (radiation works, electric shock doesn't) 2. Time between eating and nausea can be as long as 24 hours (for all other associative learning interval between stimulus and aversion must be within a couple seconds 3. Can condition aversion to a place (restaurant, etc)

Why do people eat spicy foods?

1. Rotting Hypothesis 2. Macho hypothesis 3. Eating spicy food cools the body 4. Antimicrobial Hypothesis

Summary of the role in taste in determining intake

1. Taste does not differentiate between obese and non-obese 2. Variation in taste plays a major role in determining intake 3. Variety is a positive food prime

Exercise Summary

Exercise may not help you lose weight but it's good for your health

Obesity Epidemic Summary

THERE IS AN OBESITY EPIDEMIC

Neuropeptide Y

The most powerful stimulant of eating behavior we know

Conclusion of all of Schachter's Studies: Externality theory of obesity

The obese are obese because they are less sensitive to internal cues and more sensitive to external cues

Plethera theory/Luxusconsumption

The thermic effect of food is part of a regulatory process to keep energy production in the body regular; this protects you because you blow off this extra energy during eating

Evidence against Wurtman hypothesis

There is no evidence that eating any food can cause a change in brain serotonin

VMH is

the satiety center --lesions cause overeating-- no satiety --stimulation causes cessation of eating

BMI

--Body mass Index --Weight/Height^2 --Over 30 is obese --25-30 is overweight --18.5-25 is normal --Under 18 is underweight --Not great measure of fatness because it doesn't differentiate between muscle mass and fat mass --Also doesn't differentiate between Android and Gynoid weight distributions which carry different risks

Does stress cause overeating and obesity in humans?

-- 1/3 of people say they increase their intake when stressed; 1/3 say they decrease it and lose weight --Being a restrained eater increases tendency to eat in response to stress: they gain weight even though they are restraining their eating --Acute stress changes the pattern of eating: fewer meals and more snacking-- sympathetic stress collapses GI tract function (decreased capacity of stomach to expand-- smaller meals) --Perceived stress causes an weight loss in low BMI, weight gain in high BMI, no change in the middle --LITTLE EVIDENCE THAT ACUTE STRESS CAUSES AN INCREASE IN FOOD CONSUMPTION

Neurotransmitters and feeding

-- Lots of neuropeptides can stimulate feeding --a HUGE number of neuropeptides can inhibit feeding

Levitsky's Law

--Body weight = energy in - energy out

History of thermic effect of food

--1881 Carl Voit discovered that oxygen consumption goes up immediately after eating; O2 is consumed after eating rather than during fasting --Newman in 1902: the obese have something wrong with the thermic effect of food and can't blow off this extra energy after eating

Evidence Supporting Leptin as Set-Point Signal

--2 strains of obese mice were deficient in leptin: they were obese, overate, and had a lower metabolic rate --Injecting leptin into these obese mice stopped their overeating, increased their metabolic rate and the weight normalized --Leptin is produced by adipose cells --Serum leptin concentrations are directly proportional to fat composition --Leptin blood levels drop if you starve an animal for a couple of hours (increases rapidly when you eat again) --Injected leptin reduces food intake in animals --Leptin receptors found in hypothalamic structures (defect in leptin receptors found in obese rats)

Additional Evidence for the Glucostatic Theory of Eating

--2-deoxyglucose (glucose analog that is picked up when insulin is available but stops metabolism of glucose) causes feeding in rats: if you block glucose utilization, the animal eats --Goldthioglucose (destroys areas that absorb it) causes obesity in rats: it gets picked up by the hypothalamus and destroys areas in the hypothalamus; causes obesity; insulin ENHANCES this effect (discovered hypothalamus has insulin receptors) --Glucagon inhibits eating in animals and humans: released by the pancreas in response to hypoglycemia, breaks down liver glycogen and increases blood glucose; if you inject glucagon into a hungry animal they stop eating --Insulin stimulates eating in animals and humans: first it increases glucose utilization (increases uptake of glucose from the blood into tissue), followed by a decrease in glucose utilization (it is during this phase that eating is stimulated

Drugs Treating Obesity: 1973

--3 new drugs released: fenfluramine (increases serotonin), mazindol (inhibits NE and serotonin reuptake), and chlorphentermine (inhibits serotonin re-uptake; withdrawn in England because it caused heart attacks and pulmonary conditions) --All 3 caused weight loss

Settling Zone

--A genetically determined range of body weights we can be in without making large changes --How big it is depends on how imprecise our energetic compensation is

MET

--A measure of activity gives you the amount of energy you use above maintenance of your body --(total expenditure)/(Resting metabolic rate) --Number of higher MET jobs has decreased and number of low MET jobs has increased since 1950

Energy imbalance leading to weight gain

--A small, persistant average daily energy imbalance gap between intake and expenditure exists and underlies the observed average weight gain --Is about 7.2 calories a day

Evidence against glucostatic theory of eating

--AV correlation with eating only works with carbohydrate meals --The dose necessary to cause 2-deoxyglucose eating in rats was far higher than that required to block glucose utilization --Glucagon blocks gastric emptying (slowing gastric emptying decreases eating) --Epinephrine and Amphetamine block glucose utilization AND inhibit eating --Timing of insulin induced eating not correct (eating actually begins while glucose is being utilized-- directly contradicts) --Insulin facilitates gastric dumping --Neither glucose nor insulin infusion prevents or reduces food intake --Animals and humans begin to utilize glucose BEFORE they begin eating (drop in glucose occurs prior to meal; this drop is probably due to excitement in eating; correlates with anticipation and excitement

Study: slowing development of adipose cells in rats

--Adipose cell numbers increase very early in life and then remain constant --If you slow down that rate of development when adipose cells are increasing, you have a lower number of cells that are sustained in adulthood

Thermic Effect of Food

--After a meal there is a spike in heat production (energy expenditure) and then it decreases --Reasonable because these proteins need to be broken into amino acids which requires work which creates heat --Heat increment of food = thermic effect of food = specific dynamic action (SDA) = post prandial thermogenesis = diet induced thermogenesis = increase in heat production after eating a meal

Freud and Bruch's Problem

--Both commit a clinical fallacy: they based their theories on clients that they saw as part of their clinical practice-- doesn't represent the population

Gordon Kennedy-- VMH

--After lesion, intake came down almost to normal and body weight plateaus --Said that if you destroyed the satiety center intake could not come down to normal and that could only happen if other areas took over the VMH --Experiment: lesioned animals and reduced amount of food-- lost weight because of food deprivation --Then let the animal eat as much as it wanted-- animal gained the weight back --Theory: VMH sets the level of fat content for the body and maintains it by controlling intake (lipostat in the VMH sees how much fat there is; needs to increase intake to increase signal from fat) --VMH SETS UPPER LIMIT OF FAT CONTENT

Paul Campos: The Obesity Myth

--Against the ida of an obesity epidemic

J. Oliver: Fat Politics

--Agriculture vs. health --Supporting agriculture vs. obesity epidemic

Mechanisms of Drug Actions

--All act at the synapse 1. Cause release of neurotransmitters from vesicles 2. Stimulate receptors on postsynaptic neuron 3. Block reuptake pump and conserve existing neurotransmitters

Energy Deficit Studies

--Alternative day fasting: weight loss in every study, no evidence for compensation; intermittent fasting IS effective in weight loss (but hard to sustain) --Underfeeding: no compensation; the majority of papers say you end up consuming fewer calories than if you fully compensated --Exercise: no compensation for energetic error imposed by exercise; you don't overeat after --Caloric Substitutes: compensation is under what is expected --Meal Skipping: people do not compensate for skipping a meal-- energy deficit accumulates over time

Kehauver-Harris Amendment

--Amendment to Drug and Cosmetic Act --Mandated evidence of efficacy for weight loss drugs: many were removed

Experimental Evidence for Wurtman Hypothesis

--Amphetamine increases NE and Dopamine --Fenfluramine increases serotonin --Injecting fenfluramine in mice increases brain serotonin and inhibits intake for carbs --Fenfluramine decreases snack eating and binge eating: it is an anorectic

Gut hormones

--Amylin, Glucagon, Oxytomodin, PYY, and GLP-1 are released after eating by various organs --They cause gastric emptying and nausea which inhibits appetite --GLP-1 has unusual properties and is related to gastric bypass

BAT PET Scan Study

--Analyzed PET scans to find BAT --Females have more BAT than males: peculiar because females have more fat than males --Brown fat is inversely related to BMI (larger people have less brown fat) in older people --BAT activity is related to outside temperature

VMH Lesions

--Animals become massively overweight --All the weight gained is fat tissue --They ate very large meals-- suggests that they had no satiety and had no idea when they were full (increase in caloric intake) --Became behaviorally inactive: lesions made activity drop immediately (under-exercising and over-eating) --Cause lower metabolic rate: VMH animals gained more weight than a control when they ate the same amount --Loss of motivation: will not work for food; higher intake but lower motivation-- VMH animals will overeat if they have free access to food but if they need to work for it they won't --Causes finicky eaters: VMH animals won't eat food with quinine even if they are very deprived (where control animals will) --If you stimulate the VMH the animal stops eating

Stress induced eating: Tail pinch induced eating in animals

--Animals eat fairly reliably when their tails are pinched with forceps --Activates a group of neurons that activate the lateral area of the hypothalamus: sends dopamine up the spinal cord which increase eating, gnawing, biting, fighting, drinking (any type of consumption appropriate for the animal) --Stress based dopinergic stimulation that increases all oral behaviors

Variations within a meal

--Animals eat more --As number of foods offered at a meal increases, total intake increases --Study on dessert: there is room for another course when it changes

Animal Protein intake

--Animals generally eat 20% of the weight of food as protein --The don't grow as well on a low protein or high protein diet because of decreased intake

Fevers can cause:

--Anorexia --Increase in glucagon --Decrease in insulin --Delay in gastric emptying

Stress Measure by Weight Change

--As job related demands increase: --BMI over 22.8 in men and 21.7 in women: weight decreases --BMI of 27 or higher: weight stayed constant --BMI of 34 or higher: weight increased --Larger people are more sensitive to weight gain

Social Facilitation

--As your increase the number of people eating together you consume more --When you see others eating more and more rapidly you eat more

Study by McCarthy

--Asked if it was the heat generated by the fever that causes the decrease in appetite or the cytokines --Control rats --Rats with endotoxin (fever) --Rats with endotoxin and aspirin (blocks heat) --food intake of endotoxin + aspirin rats is the lowest; intake of endotoxin rats was in the middle; control rats ate the most

Gard and Wright

--Australian exercise physiologists doing research --Pushing the lack of exercise as our problem, not eating too much --Levitsky says this is wrong

Glucose Theory of Eating

--BGL drops during the day before you eat; dropping glucose could be exacerbated by thinking about food because of the cephalic phase of digestion --You find something to eat --After we eat our BGL increases and we fee l satiated --BG is the oldest blood metabolite we thought was responsible for eating

Basal Metabolic Rate and Genetics

--Basal metabolic rate: the lowest metabolic rate that you can measure; minimum amount of calories it takes to keep you alive --Pima Indian Studies: 11% of BMR was due to familial factors; observed that infants with low BMR gain the most weight (NOT observed in other groups) --Twin studies: significant but not large correlation between BMR and twins

Non-hedonic eating

--Berridge: wanting and liking are determined by 2 different areas in the brain --Lowe and Levine: difference between needing and wanting-- you can break non-hedonic eating into various different stimuli

Study: Effect of Food Deprivation on the Obese

--In normal subjects pre-loading suppressed intake --In obese people with an empty stomach pre-loading did NOT decrease intake

Evidence against CCK

--CCK causes decrease in many behaviors such as exploration and maternal behavior, and causes increases in anxiety (not specific to satiety) --Potentiates pain: can't eat if you're in pain --doses needed for reduction in intake may be pharmacologic (much larger) and not physiologic: CCK after a meal is too small to inhibit appetite --Removing pylorus or vagus removes effect of CCK: CCK in the periphery is acting through pylorus and vagus, CNS actions are not necessary, gastric distention and gastric emptying are affected --Endogenously released CCK (trypsin inhibitor stimulates endogenous release) does NOT result in reduction in intake

Capsaicin and Weight Loss

--Capsaicin may be thermogenic but it does not cause weight loss --It raises metabolic rate, decreases appetite, and you sweat because of the increase in thermogenesis --BUT there is no evidence that it causes weight loss

What part of our diet have we been increasing?

--Carb intake has been pretty consistent; slow decline from 1900s, increase in the 1950s, decrease in the 1990s --Protein intake has been fairly constant --Fat has been steadily increasing (THAT is where you get the increase in overall calories)

Wurtman Hypothesis

--Carbohydrate hunger is regulated by brain serotonin --Low serotonin creates sugar hunger --We eat to maintain brain serotonin --Dietary sugar => insulin release => Reduction in albumin bound FFA and amino acids => Increase in tryptophan => Increase in brain tryptophan => increase in brain serotonin => decrease in hunger for sugar

Gestational Diabetes

--Causes large birthweight --High maternal glucose stimulates fetal insulin --Insulin causes storage of fat and protein in fetus

Tasting with your eyes

--Changing color of wine changes taste properties --Changing shape of wine glass changed perception of flavor --Changing color of familiar foods decreases the palatability of the food and decreases the amount eaten

Gut Bacteria

--Chew up food we can't digest --Play many roles in digestion --Germ-free mice (no gut bacteria) resisted weight gain --Genetically obese rats have lower Bacteriodes concentrations and higher Firmicutes concentrations in their gut --If you take the bacteria from obese mice into lean mice they get larger --Obese humans ALSO have lower Bacteriodes concentrations and higher Firmicutes concentrations in their gut --Overfeeding humans causes lower Bacteriodes concentrations and higher Firmicutes concentrations in their gut --Potential for using fecal transplants to treat obesity

Caloric Density Study

--Chicken rice casserole pre-load reduced intake --Chicken rice casserole served with a glass of water pre-load reduced intake more --Chicken rice soup pre-load reduced intake by a LOT --Shows that it is the energy DENSITY not the fat itself --Diluting food with water reduces intake

Relationship between breast feeding and obesity

--Children that were never breastfed have higher body weights as adults than those who were (Includes gestational diabetic infants) --Problem: mothers who choose to breastfeed are more health conscious, higher income, higher educated --CONCLUSION: Breast feeding has a small but conssitent protective effect against obesity in children

Antimicrobial hypothesis

--Commonly used spices do inhibit bacterial growth --Spices are chemicals and many are antimicrobial --In warm climates spices may prevent rotting --Higher temperature climate--> greater amount of spices used on meat (less of a correlation on vegetables but there is a slight one

Correlation in weighed intake between family members

--Correlation in higher intake in monozygotic twins; slightly lower in dizygotic twins (same as siblings) --Difference in monozygotic and dizygotic twins is pretty small

Mechanism of Action of Cushing's Syndrome

--Corticoids released causing hyperglycemia which causes insulin resistance by blocking insulin receptors (blocking of insulin receptors does not occur in the face, back and abdomen so that's where you accumulate fat) --Gynoidal distribution of weight has normal cortisol; androidal has higher cortisol levels

Peter Herman

--Created the restrained eater test to see if the obese really were below their set point --Restraint Scale: questions to figure out where you are vs. where your set point says you should be

Bottom Line About Fevers

--Cytokines do inhibit intake and are probably responsible for illness induced anorexia --Illness induced anorexia may be protective against some kinds of infections

Added Sugars

--Decrease in amount of added sugars consumed since 2000 --Slight plateau in carbohydrates consumed since 2000 --HUGE increase in added fats consumed since 2000 --FAT IS RESPONSIBLE FOR OBESITY

Gastric Bypass Mystery

--Diabetes that can't be controlled by insulin immediately improves after gastric bypass surgery --Occurs before the weight loss happens --How: when food goes into the intestine it releases GLP-1; GLP-1 increases significantly after gastric bypass because a large bolus of food hits the large intestine; GLP-1 improves insulin sensitivity remarkably --GLP-1 is now marketed commercially

Increase in energy intake can more than sufficiently account for the increase in obesity

--Dietz study on intake from NHANES: says intake has decreased --Problem: you can't remember all the food you ate; large eaters underestimate how much they eat and small eaters overestimate --The reported relationship in the study between energy intake and body weight is flatter than the true relationship --Double labelled water studies do not correlate with diet records --Se;f reported diet records are too inaccurate of true energy intake: makes people doubt the validity of science

Sugar substitutes

--Do not work --We are using more but still getting fatter --Direct correlation between BMI and sugar substitute use-- substitute usage massive increase happens at the same time as rise in body weight --Alternative explanation: larger people are seeking solutions and if they think sugarless sweeteners will be healthier they will eat them --NOT CAUSATIVE: LARGER PEOPLE USE MORE BECAUSE THEY SEEK CALORIC REDUCTION --Studies on sugar substitutes show that they decrease caloric intake

Energy expenditure of humans is not lower than energy expenditure of other terrestrial mammals

--Larger animal = larger energy expenditure --We fit along the graph of animal size vs. expenditure

Government's Proposed Solutions

--Eat more fruits and vegetables --Drink more water (and less sugared drinks) --Limit children's screen time-- no TVs in bedrooms --Have farmers markets to improve access to fruits and veggies --School health advisory councils: more PE, more healthy foods --Traffic safety, crime prevention, sidewalks --More breastfeeding: breastfed babies are more likely not to be obese ***Note: no one talked about biological/medical causes or solutions; all behavioral

Macho hypothesis

--Eating chili peppers is a sign of maturity --Children do not eat spicy food, but must learn to eat it (right of passage) --No evidence

John Brobeck: Thermostatic Theory of Eating

--Eating is determined primarily by temperature --In 1953 he suggested that SDA produced satiety (not obesity): food consumption vs. protein composition vs. SDA makes a U function (SDA is higher on high protein and low protein diets-- shows inefficiency which is translated to heat; intake is low on high protein and low protein diets because the heat production stops you from eating) --Step too far: animals eat to keep warm and stop eating to prevent hyperthermia

Other Stressors in Animals

--Electric shock produces inconsistent effects on eating behavior --Defeat in mice increases feeding --Isolation in rats increases stress and feeding --Group housing in hamsters increases stress and feeding --NO ONE HAS PROVEN THAT LONG TERM STRESS CAUSES OBESITY!!!!

Food produced per year

--Energy production per capita per day has increased --Slope: 24 calories per person per day

Ephedra/Ma Huang

--Ephedrine is the active ingredient-- stimulates sympathetic nervous system --1980s: began to be sold for weight reduction --If you have heart problems it makes them worse (raises BP, increases ulcers) --Maker was sued

Problem with Exercise

--Expenditure compensation --Your energy expenditure increases while exercising --After exercising your metabolic rate DECREASES to below energy expenditure at baseline

Selective Breeding in Agriculture

--Farmers can breed animals for a higher food intake and lower metabolic rate to maximize animal weight with minimum input --Shows that genetics can cause obesity

Food is less expensive at restaurants

--Fast food restaurants are streamlined from start to finish --They can afford to give you cheap food and still make money --It is more expensive to buy the same food at the store

Alternate Day fasting

--Fasters lose weight over 22 days --If you fast one day and eat as much as you want the next you still see weight decreases

Fat Content vs. Energy Density of Food

--Fat content is positively correlated to higher energy density in food --Greater amount of fat means greater caloric density --Fat is the most energy dense macronutrient

Eating in a restaurant vs. eating at home

--Fat content of food is higher: we can't compensate, the more calories we consume --Portion sizes are larger: the more in front of use the more we eat --Eating with more people: we watch other people eat rapidly, you eat rapidly-- increases amount of calories you eat --Variety of foods is greater: leads to greater caloric intake --Cost of eating in fast food restaurants is less than if you purchased and cooked it yourself: predictor of behavior, important for low-socioeconomic group --Effort to prepare food is less --More advertisements: restaurants are commercials

FMS

--Fat mobilizing substance/hormone --Low carb diet supposedly releases this substance that works by breaking down fat tissue --There are very few articles and if it really worked you would expect more

Jean Mayer

--Father of nutrition, endocrinologist --Said that the signal couldn't be glucose because diabetics would never stop eating --He said it wasn't glucose levels, but glucose UTILIZATION that was the stimulus to eat (the amount of glucose that is going into some cellular monitor; that is the trigger for eating --Also said that the receptor for glucose utilization (sensor) was in the hypothalamus which is a critical areas in the brain that causes obesity and anorexia --At the time it was thought that the hypothalamus was independent of the rest of the brain because it has insulin receptors

Exercise is more important than weight loss

--Fit people have much less chance of dying than unfit people of the same BMI

Food Priming

--Food stimuli come in through sensory receptor and produces not just information but also eating behavior --Not important if conscious or unconscious --Response to positive food primes: originated from very primitive behaviors (see food, eat food; comes from a time when food was not available)

Seeing food: positive food primes

--Food stimuli come in through sensory receptor and produces not just information but also eating behavior --Studies: get people together to evaluate advertisements, etc. --Food commercials result in MUCH more snack consumption --Another study: children watched programs with either non-food commercials or food commercials-- children ate more when they watched a food commercial

Taste Receptors

--Found in the tongue --Also found in the intestinal tract and we don't know why

Consumer Freedom

--Funded by the big food companies: they are worried about people eating less because they will lose money --Says that health campaigns are paternalistic and that the government should not be involved --Opposed to idea of obesity epidemic

Nutritional Programming Study

--Gambian children conceived in the wet season or dry season --There is a correlation between mother's blood and methylation of child's DNA --Mothers methyl donors are significantly correlated with the methylation of the child's DNA; methylation of genes remained in the child at least until age 5 or 10

FTO Genetic Variant

--Genetic component that has the highest correlation to body weight that we have found so far --People with no FTO vs. people with one copy of FTO vs. people with two copies of FTO: significant increase in body weight in double mutants --Significant due to high sample size: small but significant difference, may not have clinical significance

Brown Fat (BAT) Hypothesis

--Genetically obese rats die in the cold --Obese animals have less BAT: the BAT doesn't work, had less "coupling protein" --Studies of the backs of obese patients suggested less BAT --Lots of studies to see whether obesity is caused by lack of "normal" brown fat --Conclusion: human BAT may not contribute as much as thought to energy expenditure-- thermogenesis relies mostly on muscle metabolism --Human BAT studies are still inconclusive

Glucose and Eating

--Glucose is the preferred substrate for metabolism: brain and neural tissues are not insulin sensitive (totally glucose dependent) --Rises after a meal --Declines if we don't eat --Well regulated --Sugar is associated with feelings of energy (this is probably conditioned though)

Degree of Compensation Phenotype

--Greater adiposity of children, less likely the subjects adjust energy intake to energy density --if you are given a diet lower in energy density you have to eat more of the less dense energy food in order to compensate for the lower energy density of the food --Compensating in next meal for reduction in calories at another meal

Variety

--Greater variation means greater intake --More variation in veggies means less obesity, more variation in everything else means more obesity

Study: is there a biological benefit to not eating when you have a fever?

--Groups that can't reduce their intake during the fever had much higher mortality

What is special about fat that leads to weight gain

--Has a very low thermic effect of food (low metabolism increase) so none is wasted --98% of the calories are absorbed --Could be related to the caloric density of fat

Epigenetics

--Heritable changes in phenotype that do not involve alterations in the DNA sequence --These heritable changes are caused by the environment

Reinforcement phenotype

--High BMI adults show higher reinforcing value of food --Obese individuals will work harder for food

Perceived palatability phenotype

--High BMI adults show increased intake of palatable foods --They like the food more --They like good food more than low BMI adults

2 Major Mechanisms of Epigenetic Transfer

--Histone Modification to alter the degree to which DNA is wrapped: if you methylate histones you change the tightness of the DNA wrapping-- allows code to express itself in the cell --Changes on the DNA itself: DNA becomes methylated and that changes the degree to which the DNA can be expressed

Albrecht Haller

--Hunger caused by irritation of nerves located in the stomach --Walls of the stomach grinding --1776 (not accurate)

Walter Cannon

--Hunger caused by lack of gastric contractions --Had a subject swallow a balloon so any stomach movements are recorded --Concluded that hunger is caused by stomach contractions --Problems: stomach contacts when food stretches the stomach and the balloon stretched the stomach, and hunger was the dependent variable and hunger does not actually correlate with how much we eat

Two Types of Obesity

--Hypertrophic: adult onset; people with very large adipose cells-- people consuming more than expending --Hyperplastic: child onset; born with many more adipose cells; very difficult to treat --Based on the fact that the number of adipose cells remains fairly constant throughout a lifetime

How important is smell for consumption?

--If you cannot smell (intranasal lidocaine) your hunger ratings and desire to eat increases --Smell does NOT affect how much you eat

Balancing Amino Acids

--If you disturb the natural ratio of amino acids in the blood (ex: increase Histidine), the animal inhibits appetite --If you alter the natural ratio of amino acids in the blood (ex: DECREASE histidine), the animal inhibits its appetite

Variety between days

--If you eat a greater variety of foods in a 3 day period, the caloric intake also increases

Monotony Effect

--If you eat the same food all the time you will eat less of it --Eat anything diet: pick your 3 favorite foods and only eat those

Does exercise prevent age related weight gain

--If you exercise over 7.5 hours a day your body weight is relatively constant with a slight increase --Those who exercise between 7.5 and 12 STILL have an increase --Those who exercise over 21 hours a week STILL have an increase --Increasing exercise did not prevent weight age related gain --Weight gain IS related to amount of exercise but exercise does not completely block it --NO

Studies on Fructose and Disease

--If you infuse fructose into the liver you can cause damage; artificial studies --When fed diets high in fructose vs. high in sucrose there was no effect on: weight gain, blood pressure, uric acid formation (gout), glycemic control, or blood lipids

Ventromedial Nuclei of the Hypothalamus

--If you lesion both we see a huge increase in body weight and food intake after the procedure; body weight hits an asymptote --Lesions can produce massively overweight rats

Ketone bodies

--If you lower carb intake then your body will produce ketone bodies that will feed your body and you use them as energy --You blow off ketone bodies and also lose them in the liver --Theory: the reason low carb diets work is because you lose ketone bodies in the urine --TOTAL AMOUNT OF CALORIES LOST AS KETONE BODIES DOES NOT ACCOUNT FOR THE WEIGHT LOSS ON A LOW CARB DIET

Animal Studies with the Stomach

--If you put food into the animals stomach with a cannula they will stop eating --If you take food out they start --Problem: is the animal not eating because they are full, or because they are sick --We know that it is putting food into the stomach, not nausea

Other evidence against BAT theory of obesity

--If you remove BAT in young rodents they still get fat --Cannot activate BAT without activating all the sympathetically controlled organs (they are all wired together): if anything all these organs are suppressed after eating --The amount of energy produced by human BAT is very small

Effect of lipectomy on rats

--If you surgically remove fat and it lowers the number of fat cells but NOT lower overall fat content --Other areas of fat compensated

Effect of memory on food consumption

--In order for variety to have an effect, you have to remember what we ate --Study: students eat less of second snack if they consumed the same snack earlier in the day --H.M (no hippocampus, no memories) was given 2 lunches back to back and he ate the same amount each time because he had no memory of it (discredits physiological intake control)

Social ideals of body size change over time

--In the 1600s paintings of obese women are present --Large people were looked favorably upon in history --However, simultaneously there was a corset order in France, so have ideals really changed?

Does sugar cause obesity

--Increase in carbohydrates consumed correlated with increase in obesity --But THEN carbohydrate intake began to go down but body weight did NOT (fat intake is constantly increasing) --INCREASE IN OBESITY DOES NOT FOLLOW CONSUMPTION OF SUGAR OR CARBOHYDRATES

Exercise and Lipid Turnover

--Increase in lipolysis of adipose cells during exercise --When stressed but not exercising the sympathetic nervous system is activated, lipolysis releases fatty acids and then the liver RETURNS the fatty acids to the adipose cell: circulating these fats through the blood stream is a main source of atherosclerosis: stress is much more hazardous for you than exercise --When you are active those fatty acids go to the MUSCLE tissue and are used up

Relationship between BMI and Mortality

--Increase in mortality as we get larger --Increase in mortality is smaller if you are just overweight vs. obese

Correlates with Early Adiposity Rebound

--Increased BMI throughout life --Increased risk of diabetes --Increased risk of hypertension

Effects of Exercise on Neurotransmitters in the Brain

--Increases almost all neurotransmitters (increases production and degradation-- increased turnover) --Depression: rate of neurotransmitter turnover is suppressed and correlated with feelings of depression-- characteristics: low turnover of neurotransmitters, helplessness, lack of movement --Exercise alone causes a decrease in depression scores: exercise causes a BIGGER decrease than antidepressants, cognitive behavioral therapy, and unpublished antidepressants --Increases neurotransmitter turnover and acts as an antidepressant

Exercise stimulates growth hormone release

--Increases muscle synthesis --Increase in lipolysis --Increase in muscle to fat ratio (muscle up, fat down) --Muscle has a higher metabolic rate than fat tissue

Why does eating the same food turn off eating?

--Increases the chance of getting a nutrient deficiency (thiamin deficiencies increase the amount of foods a rat will try-- usually we don't like trying novel foods because toxins) --Eating a wide variety of foods means you get a wide variety of nutrients

Energy Surfeit Studies

--Increasing energy density: increase the fat content-- people do not respond by consuming less if you increase the fat content of the diet-- no compensation --Increasing portion size: increasing amount of food on your plate increases how much you eat-- you don't compensate by eating less --Overfeeding: average intake in recovery period was equivalent to baseline intake-- no decrease in intake --NO COMPENSATION

Evidence supporting CCK hypothesis

--Infusions of CCK in the brain reduces intake (doses are lower than injections into the periphery) --In animals CCK peripheral injections reduce food intake --Antibodies to CCK receptors elicit feeding in sheep and rats: the antibodies bind to CCK receptors and prevent CCK binding --Anorectic agents like fenflueramine and serotonin bind to CCK receptors and cause inhibition of appetite --CCK antagonists block CCK inhibition of food intake

Issues with pre-load studies

--Inhibition of eating behavior after a pre-load may not be the same thing as inhibiting eating until the next meal --Preloading stretches gastric receptors --Depends on the rate of gastric emptying

Stress and digestion

--Inhibits salivation --Decreases gastric stretching --Decreases pancreatic juices --Decreases intestinal motility --Decreases insulin secretion --Blocks insulin receptors --INHIBITS ALL DIGESTIV PROCESSES --Stimulates gluconeogenesis --ANTITHESIS OF WHAT HAPPENS AFTER YOU EAT

Study: Rat eating an imbalanced diet

--Intake slowly goes down on a normal diet --On an imbalanced diet they start off normally but decrease intake much earlier-- total intake is less --Rat eating an imbalanced diet but infused with the missing amino acid: looks like a normal diet

Dexfenfluramine

--Introduced in 1996 despite animal studies showing neurotoxicity --Restricted to BMI>30 or BMI> 25 with complications --Wildly successful --Caused valvular heart disease which resulted in litigation because the companies knew about the animal studies

Rimonabant

--Introduced in 2006 --Blocked cannabinoid receptors --Blocks appetite and induces weight loss --Rejected in US due to increase in psychiatric disorders and suicides while on it

Sibutramine

--Introduces in 1997 --Blocks serotonin and NE re-uptake --Reports about adverse cardiovascular effects especially in those with diabetes and arterial disease (correlated with obesity) --Withdrawn in 2019

Leptin Receptors

--Isolated in the LH and the paraventricular nucleus (PVN) and arcuate nucleus --The leptin receptors in the VMH and arcuate nucleaus inhibit eating --In the LH they stimulate eating --Both seem to operate with neuropeptide Y

Dieting may cause overeating

--It increases metabolism (?) --Causes eating disorders: bulimia is more likely in restrained eaters (but also cognitive distortion causes dieting which causes bulemia)

Is BAT the locus of diet induced thermogenesis (TEF)?

--It would need to be activated after eating --Problem: BAT is sympathetically innervated and eating ins parasympathetically mediated

Problems with LH as feeding center

--LH lesions cause vagal inhibition: lack of salivary secretions, lack of stomach acid secretion, lack of gastric motility-- all of the above will push off eating behavior --LH stimulation causes and increase in many behaviors: drinking, fighting, copulation-- LH stimulates any appropriate behavior based on the environment --LH stimulates dopaminergic tracts: explains self-stimulation (reward centers); responsible for repetitive behavior

Mechanism for the Obesity Paradox

--Larger bodies have more lean body mass; the larger you are the more muscle you need --The greater the lean body mass, the greater the amount of heart tissue --The amount of tissue on the heart maintains it through the recovery period --Large people --> larger muscle mass --> more heart muscle--> better survival

Arcuate Nucleus (VMH)

--Leptin inhibits NPY release --Leptin stimulates POMC (POMC inhibits eating by inhibiting NPY) --Agouti protein inhibits POMC: Agouti mice that produce excess Agouti protein and are very obese --Ghrelin stimulates NPY and Agouti protein --Other orexigenic hypocretins (Orexin-A, etc.) stimulate NPY

Richard Keesey--LH

--Lesion the animal and it becomes anorectic; after a while body weight stabilized --If you first deprive the animal before you lesion them and you reduce them to the body weight they would be with the lesion you do NOT find a decrease in intake --LH SAETS LOWER LIMIT OF BODY WEIGHT

Lateral Nuclei of the Hypothalamus

--Lesioning the LH produces aphagia --Stimulation causes animals to eat

Clara Davis Study of Children

--Let children choose their own foods-- they grew well choosing their own food --Conclusion: children have innate nutritional wisdom and know what to eat --Problems: cannot prove null hypothesis AND child only had access to nutritious foods, no junk food

Percent calories as fat vs. body weight

--Linearly correlated

Daily Physical Activity and Genetics

--Little data available --Finnish twin study: calculated that identical twins have a closer correlation of activity levels than fraternal twins

Cue Reactivity Study

--Look at how much people eat or weight change based on certain cues --Tendency to eat in response to food cues vs. non-food cues; same for weight gain

Study Proving the Glucostatic Theory of Eating

--Looked at various infusions of things directly into the bloodstream --Measured AV difference: difference between glucose in arteries and veins (should be a predictor of hunger) --Conclusion: the AV difference correlated highly with the subject's rating of satiety: AV difference was inversely correlated to hunger and could cause eating and satiety

History of Low Carb Diets

--Lots of books; started in the 1960s --Very old idea

Do we compensate for not eating breakfast?

--Lots of studies say that people who eat low or no breakfasts have a higher BMI --Implies that skipping breakfast stimulates intake --Alternative explanations: --People concerned with their weight skip breakfast (the amount you overeat for lunch is MUCH less than the meal you skipped; you DON'T compensate; breakfast skippers have a lower overall intake) --People who eat breakfast are more active --NO

Effect of Exercise on Food Intake in Humans

--Lots of studies: some find it inhibits food intake, some find it stimulates, some say it has no effect --Most literature shows that low intensity exercise has slight inhibition of intake, medium intensity there is no effect, high intensity (olympic athletes) increases daily food intake

Judy Rodin

--Lots of work on obesity --Studies on the externality theory-- do normal weight individuals respond to external cues? --Wiped out the obesity part of the externality theory --ALL individuals respond to external cues for eating --Said the obese were less sensitive to internal signals (rather than hypersensitive to external signals)

How large is the caloric imbalance

--Males gain 0.47 kg a year: 9.9 excess calories a day --Females gain 0.3 kg a year: 6.3 excess calories a day

Restrained Eaters

--May be an awareness of an individual's tendency to gain weight

Genetics DOES play a role in obesity but how much?

--May contribute about 50% to the variance in BMI and less to the behaviors that affect energy balance

Carlson's dog experiment

--Measured amount of movement in dog stomachs --If you take a hungry animal and infuse glucose into it, the amount of stomach contractions decrease (at this time feeling hungry was related to stomach contractions) --If you put insulin into not hungry dogs, it induces stomach contractions (infusing glucose blocked this effect) --Hypothesized that blood glucose is the mechanism that monitors our eating behavior

1931: Strang and McClugage say that satiety may be casued by SDA (the increase in heat production after a meal causes satiety)

--Measured change in skin temperature; you feel warmer after eating a big meal --Fasting temperature: decreases a little --Non-obese people after a meal: skin temperature increases quite a bit --Obese people after a meal: do not show this increase in temperature --Conclusion: Obesity caused by blunted SDA (TEF)

Metabolic Hypothesis

--Metabolic advantages that allow overweight individuals to eat as many or more calories than they were eating before and still lose weight --Increase in metabolic rate attributed to food --Diet makes you less efficient and makes you burn off excess calories --Thermic effect of food: greater protein intake means more TEF --You blow off more ketones --You supposedly release more fat mobilizing substance

CCK and obseity

--Mice that don't express CCK receptors are obese --Genetically obese rats have decreased CCK sensitivity --Obese humans do NOT have lower levels or lower sensitivity to CCK --Anorectics show high levels of CCK --Low CCK has been found in bulimic patients

Alliesthetic Theory of Obesity

--Michael Cabanak --Tracked Hedonic ratings (sweetness) of lean and obese adults throughout a meal --Obese individuals never had the food become less appetizing

Correlation in BMI between twins

--Monozygotic twins: 0.7 correlation (still only accounts for half of the variance) --Dizygotic: 0.3 correlation --Shows that there definitely IS a genetic correlation --Twin correlations depend on the age at which you measure; degree of correlation goes down with age: influenced more by environmental factors as you get older, heritability constant decreases with age; non-shared environmental factors in twins increase their effects on obesity over time

Clinical Studies of Changes in Dietary Fat and Body Weight

--More studies have found that body weight is related to dietary fat than have found it is not related --Pretty good linear relationship linking weight loss to reduction in dietary fat in studies where they experimentally change the amount of fat in the diet

Arguments against Set-Point theory

--Neurochemicals that affect eating are not behaviorally specific --There is no signal/feedback from fat (leptin is not the feedback and we can't find any other feedback) --Cannot account for secular trends in obesity: why would we be getting fatter all over the world --Cannot account for migration studies: people who go from Hawaii to Japan get thinner and vice versa --Suggests that the solution must be biological/pharmacological

Paraventricular Nucleus (LH)

--Neuropeptide Y (NPY) is a powerful stimulant of eating --Increase in NPY just before eating --Secretion continues as long as the animal is not fed (continues to be secreted even when not eating) --If you block NPY receptor the animal won't eat --Small doses of insulin suppress NPY production

Gelesis

--New weight loss drug --Used in conjunction with diet and exercise --Absorbs water to create a larger volume in the stomach and increase gastric stretch --Shows significant weight loss over time

Do we compensate for fasting?

--No increase in intake after fasting --You do recover weight after fasting though: you lose lean body mass when you fast which reduces energy expenditure --No indication of any compensation for fasting but you still make up the body weight by passively changing energy expenditure

We are more active than ever

--Non-active leisure time has decreased since 1985 --Lifestyle and leisure time energy expenditure has increased

Problems for a Physiological Theory of Eating

--Non-homeostatic eating: we eat for reasons other than to maintain a homeostatic balance --Stability of body weight does not mean weight regulation: theory-- weight is controlled by weight (intake is random, some days you eat more, others less around a certain mean; expenditure is random, some days you exercise more, others less around a certain mean) --The above would keep body weight constant because both hover around a mean of 2000 calories a day --The larger you are the greater energy expenditure: 25% of weight gain is metabolically active muscle tissue; need more calories to move a larger mass --Imprecision of control of intake: intake doesn't compensate for error well; you don't make up for the missed calories if you skip a meal

Study: Fear Used as Internal Signal

--Normal people had much less intake with high fear --Obese people had more intake with high fear --Supported the idea that the obese were not sensitive to internal state of fear; supports that the obese can't read internal states

How well do feelings of hunger correlate with the amount consumed

--Not well; Hunger ratings are useless (based on Cornell study) --Correlates poorly with intake (kcal or volume) --Can't measure it directly or compare it --Hasn't told us anything about how to control intake --Unit of analysis is the meal (could correlate to 24 hour intake, we don't know)

James H. Meyer

--Noticed that low protein fed rats were smaller but had a greater fat composition --Suggested that they couldn't eat more because they couldn't dissipate the heat caused by eating carbs (high carb diet makes fat)

Yom Kippur Study

--Obese Jews spent more time in synagogue than thin Jews --There were no external signals around to eat so the obese would be able to keep fasting if they stayed in synagogue --Non-obese people would wander out of the synagogue because their internal clock could not be tricked

Food responsiveness phenotype

--Obese children are much more responsive to food (palatability, time of eating, etc)

Portion Size Effect Phenotype

--Obese children show increased portion size effect --Greatest predictor of how much you will eat is how much is on your plate

Prevalence for Adult Obesity as function of childhood obesity

--Obese children under 12: small correlation with adult obesity --Obese children over 12: large correlation to adult obesity

Evidence against leptin

--Obese humans have more leptin than non-obese (leptin resistance): leptin concentrations are proportional to body fat --Leptin concentrations increase during pregnancy but intake doesn't decrease --Huge variability in human leptin levels --Fasting causes greater decrease in leptin than decrease in body weight --Leptin levels are lower during weight loss than weight maintenance (should be proportional to the weight) --Refeeding causes immediate return of leptin levels before the return of body fat --No effect of feeding high fat diet on leptin despite change in body composition --Post-prandial levels of leptin don't correlate with hunger or satiety --No correlation between genetic disturbances of leptin and degree of obesity we find --"knock-out" mice without NPY are normal weight --Leptin injection does not suppress body weight in obese men --Leptin doesn't cross blood brain barrier well --Half-life of endogenous leptin is very short

Anticipation phenotype

--Obese people show enhanced salivation at the presentation of food

Correlation between Depression and Obesity

--Obese women have higher rates of depression than men --Depressed women: 10%; depressed obese women: 14% --Obese women are 40% more likely to be depressed than non-obese women --Extreme obesity is linked to greater risk of psychological stress than moderate obesity --In early adolescence obesity and depression were independent --One year later depressed girls were twice as likely to become obese; in late adolescence depressed boys were LESS likely to be obese --In older adults, the depressed were at 32% greater risk of obesity --Depression incidence was 79% greater than the obese --OBESITY CAUSES DEPRESSION AND DEPRESSION CAUSES OBESITY

Energy Cost in Jobs over time

--Occupational expenditure has decreased by 100 cal per day

Stimulation and Nutrition in Intestine: Henry Koopmans

--Sewed 2 animals together and crossed their intestines --acute stimulation of the duodenum does NOT suppress intake of double duodenum animal --Chronic ileum stimulation DOES suppress intake (stimulation without nutrients) --Infused nutrients don't reduce intake --Conclusion: the signal to stop eating comes from somewhere in the gut and something causes satiety

People DO lose fat on low carb diets. Why?

--On a low carb diet there is water loss due to less glycogen: it is very heavy on high carb diets because it is glucose combined with water --A decrease in carbs also increases the amount of sodium lost by the kidney: loss of sodium means loss of water which means loss of weight --Actual reduced energy intake: Reducing carbohydrate intake reduces the total caloric intake because there is no caloric compensation-- if you reduce one component of the diet you don't compensate by eating more of something else; some ketosis; high amino acid concentration (as amino acid concentration increases intake goes down); reduces food variety

Currently approved drugs

--Orlistat: inhibits pancreatic lipase; can't break down triglycerides in food or absorb them --Lorcaserin: blocks 5HT2C serotonin receptor; has some side effects --Phentermine and Topiramate: used to treat epilepsy and migraines-- lots of side effects --Naltrexon and Bupropion: narcotic antagonist and antidepressant respectively (NE and D re-uptake inhibitorl nicotinic receptor (parasympathetic) antagonist) --Liraglutide: GLP-1 receptor agonist; lots of side effects

National Weight Control Registry

--People register who can reduce and maintain their weight --People can do studies to see what makes a successful dieter --Must be 18 and have lost and maintained 30 pounds or more for one year or longer --Found that successful dieters show higher restraint scores; people who are successful at reducing and maintaining their weight show greater restraint

Effect of high and low energy pre-loads on habitual exercisers vs. not exercisers

--People with high caloric pre-load who exercise moderately or a lot regulate their intake later --Those who don't exercise regulate worse --Preloading is probably not that important to weight control

Portion Size

--Perhaps most powerful external signal --Study: if you increase the amount on your plate you tend to eat more --Very robust phenomenon-- many studies --When portion size is doubled intake increases by 35% --Trends in fast food restaurants: maximum sizes have increased enormously-- Portion size and the value people think they are getting are a parameter people use when deciding to go back to a restaurant

Subjected to advertisements at restaurants

--Pictures of food make you want to eat food

Amylase blocker

--Prevents you from absorbing carbohydrates and therefore you absorb fewer calories --A substance produced by green beans is a good starch blocker but there is little if any evidence showing that it is effective at weight loss; not adequate evidence

Who profits from obesity

--Print media (book industry, websites) --Pharmaceutical industry (sell countless worthless "cures" and diet pills) --Weight loss programs: transfer to the food industry, weight watchers, hospitals have weight loss programs run by corporations --Medical industry: bariatric surgery makes money --Food industry: weight loss foods, advertisements, restaurants --All of their motives is not to promote health, it is to make money

Probability of Obesity with obese parents

--Probability of obesity increases as the amount of obese parents increases --Parents also RAISE their children so environmental factors also play a role

Ghrelin

--Produced and released by the stomach --Increases just before you eat breakfast and then dramatically decreases --Increases just before lunch and dinner too --If ghrelin drives eating, then if we block it it can casue weight loss

Prader-Willis Syndrome

--Prototypic genetic expression of obesity in terms of behaviors --Caused by hypothalamic damage --Mental issues --Deletion/damage of chromosome 15 --Powerful obsession with food --Brain never signals when they're full; always hungry, always thinking about food

Does fiber decrease intake?

--Psyllium and bran slow consumption --Fiber slows daily calorie consumption --Soluble fiber causes weight loss but not by much, by grams a day

Does rate of eating correlate with obesity

--Rate of eating is a determinant of how much you eat --In study: the faster you eat, the larger you are (weight) --A device to monitor the rat of eating: if you slow down your rate of eating (follow device beep) you eat less (study funded by device inventors)

Non-homeostatic eating

--Recognized in the past 20 years --We don't just eat in response to physiological stimulus; non-physiological stimuli push you to eat too (emotions, etc) because the nucleus accumbuns receives signals from both the thalamus AND the limbic system) --Lots of signals come from all over to feed into the nucleus accumbens which then feeds signals to the hypothalamus: very complex --Reduces physiological signals as the determinate of body weight; no unique mechanism to control eating behavior

CCK (Cholecystokinin)

--Released in the duodenum after a meal --Stimulates the pylorus to close: inhibits gastric dumping --Inhibits food intake in many animals --Stimulus for CCK release in duodenum is duodenal stretch and large fatty acids in the duodenum --Effects in intestine: pylorus closes, gall bladder constricts releasing intestinal hormones and bile, pancreatic release of digestive enzymes --Also found in the brain: stimulus for release is intragastric meal; food deprivation lowers brain CCK --Effects in brain: decrease in feeding --Receptors for CCK found in the pylorus, vagus nerve, hypothalamus, and other brain structures

Cushing's Syndrome

--Result of prolonged treatment with glucocorticoids (used to treat a number of inflammatory diseases) --Administered cortisol suppresses pituitary ACTH release which results in reversible bilateral adrenal atrophy --Characteristics: hump back (fat development in upper back; buffalo hump), moon face (rounded face because of adipose tissue enlargement), trunkal obesity (abdominal fat increases) with slim arms, red-purple abdominal striae and poor wound healing (due to lack of collagen deposition)

Robert Nisbett

--Said the obese were beneath their set-point and their behaviors were a consequence of them trying to hold themselves below their set point

Cognitive Psychology

--School of psychology that deals with what is in your head-- more interesting than counting responses

Drugs treating obesity: 1940s through 60s

--Several amphetamine derivatives approved --Enhanced norepinephrine and dopamine --Side effects: sleeplessness, anxiety, abuse of drugs: they introduced drug combos with barbituates to mediate these effects --1959: phentermine introduced-- released serotonin

Mark Friedman

--Showed concentrations of glucose infused into the brain that are necessary to prevent eating are far higher than doses infused to the liver (liver more sensitive to glucose than brain) --Infused fructose has no effect on the brain, but reduces food intake when infused into the liver --Initiate feeding with substance that blocks glucose utilization at lower doses in the liver than the brain --Said it might not be glucose or glycogen in the liver but rather ATP production (if ATP goes down, eating occurs) --You can also initiate feeding with substances that block fatty acid oxidation by the lover --Liver senses ATP formation: when ATP concentration is low, feeding is initiated --ATP concentrations in the liver fluctuate unlike other tissues

Rotting Hypothesis

--Spices can hide the taste of rotting food

Janet Polivy

--Studied eating disorders --Study: unrestrained eaters ate less ice cream when they had more milkshake pre-loads --Restrained eaters ate MORE ice cream when they had more milkshake pre-loads --Said that that is exactly what bulimics do: when they eat a little food they cannot stop

Stanley Schacter

--Studied emotions: cannon-bard (if we perceive a frightening stimulus, that activates the limbic system and then the limbic system causes changed in our body which activates the sympathetic nervous system which is experienced as fear; signal DIRECTLY creates fear) vs. james-lange (frightening stimulus activates the sympathetic nervous system then our brain interprets it and gives it a label) --Impressed by study on gastric motility: the obese seem to be unable to monitor their gastric motility --Suggested that the obese were obese because they couldn't feel the gastric contractions: they overeat because they cannot read the internal signals telling them they are satiated --Also suggested that the obese were overly sensitive to external (visual) signals

Jean Mayer (Glucostatic theory of eating guy) and exercise

--Study in rats that maps daily caloric intake vs. body weight --Animals were exercised --Decrease in body weight for exercise up to an hour-- suppression of food intake --After an hour of exercise body weight is held relatively constant and intake increases proportionally-- matching of energy intake to increased energy expenditure --After 6 hours you see the exhaustion and intake fall off and body weight falls off --If you are sedentary there is no regulation; if you exercise there is regulation of body weight --Body FAT decreases with exercise even as body WEIGHT stays constant --We only regulate our energy intake if we expend energy; most of us have very sedentary jobs

Liposuction

--Study: After a while after liposuction you regain enough weight that there is no significance --Another study: change in fat content after 6 weeks was significant; after 1 year all the weight had been gained back

Exercise and Mortality

--Study: Unfit people with BMI 25-27.9 have lower risk of death than those with a lower or higher BMI; fit people have lower risk of mortality than unfit people AND mortality is the same across all BMIs-- exercise ameliorates this effect of being very thin or very fat --IF you exercise in both the beginning and end of your life you have a lower risk of death; if you exercise in the second half of your life there is significant suppression of mortality --If you are unfit the chances of dying increase with age

Drugs Treating Obesity: 1992

--Study: low dose of fenfluramine (acts on serotonergic system) with phentermine (sympathetic stimulant) produced a 16% reduction in weight that was sustained after diet therapy stopped --If you stopped taking it all the weight was re-gained

Biggest Change In our Eating Habits: we eat more foods prepared outside the home

--Study: since 1980s people have increased how much they spend on foods prepared outside the home --We eat foods prepared at home less; disrupts the eating patterns --Change from eating in home environment to eating in outside environment --Study: steady increase in number of new restaurant per year since 2000

Fructose

--Sugar is glucose + fructose --Fructose is the class of carbohydrates showing the highest rate of consumption over time: chemists made very sweet substances with pure fructose --Used as a sweetener of snacks and soft drinks --Increase in intake of high fructose corn syrup until 1998; increases in body weight parallels with it --BUT fructose consumption went down after 1998 and body weight continued to increase --Little evidence that fructose is handled differently by the body than glucose --INCREASE IN OBESITY DOES NOT FOLLOW INGESTION OF FRUCTOSE

History of Research on the Brain and Weight Control

--Switch from thinking the hypothalamus is important for obesity to the pituitary, then back to the hypothalamus

Thermostatic Theory of Eating Brilliance

--Temperature may be the way animals sense calories --Animals and humans regulate their caloric intake via temperature --Study: animals in a hot environment eat less than animals in a thermal neutral zone; animals in the cold eat more

Study on James Meyer's Theory that low protein rats can't dissipate heat and that's why they are fat

--Tested hypothesis by increasing energy expenditure (giving the animal a way to expend the heat): if you raise an animal at room temp they eat less than if you raise them in the cold --Hypothesis: at normal temperature because they cannot blow off the heat they have excess fat; in the cold they have a way to blow off the heat --Results: in room temp the animal on a low protein high carb diet consumes less than on a control diet --In the cold the difference is reduced-- suggests that he is right and that the limiting factor is the ability to dissipate heat --Body weight shows the same trend (difference between low protein diet and control is large in room temp and small in the cold --HEAT PRODUCTION PLAYS A MAJOR ROLE IN DETERMINING INTAKE

Obesity Trends since 1960

--The amount of overweight people has remained constant, it is obesity and extreme obesity that is increasing --People susceptible to obesity are most affected by the epidemic; those with propensity to become larger are getting larger

Study: Effect of Time on the Obese

--The clock in the room either said 5:20 after 20 min or 6:05 --Normal subjects did not increase their intake when the clock said 6:05 --Obese people ate twice as many crackers when the clock said 6:05 as when it said 5:20 --Non-obese ate at the same time regardless of clock time; thought the crackers would spoil their dinner --Supports that obesity is from being oversensitive to external cues and undersensitive to internal cues

Studies comparing body weight and carb intake

--The majority failed to find a correlation with carb intake and body weight --Almost no statistical difference between people who consume more carbohydrates and body weight (unlike fat) --Body weight is not related to carb intake

Taste affect on Intake

--The obese overeat salty foods, no difference in other foods --Static obese people had no difference in sweetness rating than normal people --Fluctuating obese people have higher sweetness ratios than normal --In normal people as you continue to eat the food becomes less appetizing --In obese people there is no decrease in hedonic ratings-- the food never becomes less appetizing

Mauricio Russek

--The signal is not glucose, it is liver glycogen --Introduced the idea that eating behavior was caused by the liver --Suggested that glycogen receptors in the liver signaled the brain --Glycogen levels rise after eating and then diminish with deprivation --Neural mechanisms sense liver glucose and send information via the vagus nerve --First to show that glucose infused directly into the liver suppresses intake in dogs

Things the Government Says is Contributing to Obesity

--The way we eat has changed: more processed foods, people eat out more regularly, we are surrounded by food --Larger portion sizes --People who live in poorer areas have less access to grocery stores that have healthy options --Technology and community development (more driving, unsafe to walk) are causing a more sedentary lifestyle --We spend a lot of time sitting in front of screens --Not enough PE in schools

Genetic influence on obesity

--There IS one, people argue about how much --40-70% of variance can be accounted for by genetics --alterations in DNA expression can occur at almost any point in life and can remain that way throughout your life and will be passed through generations

Animal Genetics and Obesity

--There are many strains of obese lab animals --Obese animals can be produced by knocking out or over-expressing certain genes related to metabolism --All animals bred for obesity have: higher food intake, lower resting metabolic rate, less active, become diabetic, and have endocrine abnormalities

Genetically Determined "Settling Zone"

--There is a genetically determined settling zone; within this zone there is a range of values determined by the environment --You can control the values in the set range enough to avoid medical complications

Summary: Compensation

--There is no compensation; you only compensate by 25%

Bottom line on Metabolic Hypothesis

--There is no significant difference between a low carb and a high carb diet --NO GREATER WEIGHT LOSS ON A LOW CARB DIET --METABOLIC HYPOTHESIS IS NOT SUPPORTED

Glucocorticoids and feeding behavior

--There is some evidence that glucocorticoids increase feeding behavior in humans --Intake is difficult to measure though

Thermic Effect of Food and Genetics

--Thermic Effect of Food: rise in metabolism that occurs after you eat --Twin study: Correlation between identical twins was higher than fraternal twins-- there could be a relationship between genetics and thermic effect

Birthweight and Adult Weigh

--Those born at the optimum birth weight has the lowest adult weight --As birth weight is increased or decreased adult body weight increases

Michael Lowe

--Took the restrained eater idea and criticized it --Found that the facts were against restrained eaters as a concept --Restrained eaters don't eat less than unrestrained eaters --Restrained eaters are not at their lowest weight --Restrained eaters have a greater tendency to gain weight than unrestrained eaters

Can Adult Obesity be prevented?

--Treatments (all directed at the school): increased physical activity, decreased sedentary activity, increased nutritional information --Most prevention programs did not produce any prevention of weight gain

Blocking Absorption of triglycerides

--Triglycerides have to be broken into fatty acids before they are absorbed (lipase does this; it's released by CCK) --Blocking lipase blocks absorption of fat and blocks calorie absorption --Xenical (orlistat or lipitor) is a drug that blocks pancreatic lipase: slow weight decrease, cholesterol decrease; looked like a successful drug you could take over a long period of time --Only problem was that the dose was 120 mg and you needed a prescription; Pfizer sold a lower dose OTC but the 50 mg had NO EFFECT; prescription drug DOES have effect --When you block lipase you block absorption of fat soluble vitamins --Xenical has some pretty nasty side effects: fecal urgency, flatulence, diarrhea, fatty stools, increased defication --There's other fat blockers too but they don't have affect

Glucocorticoids

--When stressed the brain sends a signal to the pituitary that signals (ACTH) to adrenal glands that release glucocorticoids that go back to the pituitary and hypothalamus --Injecting glucocorticoids into people with injuries facilitates healing-- common treatment to ailments

Small Intestine Sham Feeding Study

--When you put food into the duodenum the animal stops eating which implies a mechanism in the small intestine that controls satiety

Does composition matter

--Yes --We eat more food if they are discrete categories (European) and less if it is a composite meal (stew, soup, etc.)

Imprecise Energetic Compensation

--You do not make up for energy deficits in one meal in other meals (biologists say you should): meal skipping, underfeeding, alternate day fasting, exercise, caloric substitutes --You do not make up energy surpluses in one meal in other meals by eating less: portion size, food composition, overeating

Variety

--You eat less with less variety --When you eat composite foods you eat less --You eat more when you have access to more flavors of ice cream --As the number of unique food consumed over 3 days increases so does your caloric intake --New foods introduced into the market per year has increased since 1980

Absorption Blockers

--block the absorption of food by the intestine --Endobarrier: a plastic tube placed into the intestine that prevents absorption of nutrients, makes your brain think you're full, causes a release of glucagon; leads to diarrhea or constipation

Eating out of the home vs. eating at home

1. Energy consumed is higher 2. Fat content of food is higher (increases caloric intake) 3. Portion sizes are larger 4. Food is less expensive 5. Food is delivered faster with little effort 6. You eat faster (how fast you eat determines how much you eat) 7. Eating with more people 8. Subjected to advertisements 9. Eating time less regular 10. We don't have mechanisms to calorically compensate

Differences in energy expenditure CANNOT account for the obesity epidemic

1. Energy expenditure of humans is not lower than energy expenditure of other terrestrial mammals 2. Energy expenditure of more primitive living people is not higher than contemporary people 3. Energy expenditure measured by double labeled water of humans has not changed for the past 30 years 4. We are more active than ever 5. Increase in energy intake can more than sufficiently account for the increase in obesity

Arguments against Ghrelin being involved in eating

1. Ghrelin knock out mice have normal body size, body composition, and food intake 2. Injections still stimulate intake 3. Appears to be inversely related to insulin concentrations 4. Infusion does not stimulate food intake in vagotomized human subjects --Vagus nerve innervates stomach and liver; it blocks ghrelin induced eating (ghrelin probably acts through the vagus) --Stimulating this nerve could treat obesity: epileptics with stimulated vagus nerves lost weight; vagus could take signals from liver and stomach and tell you to stop eating --People of larger weight lost weight with vagal stimulation-- no control group though

2 Fundamental Behavior Mechanisms Responsible for the Obesity Epidemic

1. Imprecise Energetic Compensation 2. Food Priming

Arguments in favor of Ghrelin being involved in eating

1. Secreted by the stomach 2. Increases just prior to eating 3. Infusion with Ghrelin increases food intake (causes increase on 230 kcal; proves ghrelin is stimulating the eating) --Problem: ghrelin injections started early and continues throughout the day, but usually there is just a burst; The concentration of blood ghrelin has to be reaaaaalllllly high for you to eat more --Mechanism may be stimulating gastric emptying 4. Also could be related to body weight regulation --Negatively related to body weight --When obese lose weight, concentration increases --When anorectics gain weight concentration decreases

LH is

Feeding center --Lesions cause anorexia --Stimulation causes eating

Effects of Endotoxin injected in humans

Increase in endotoxin leads to decrease in food consumption

Intake vs Expenditure Summary

We are eating too much and that is causing obesity epidemic (Not too little exercise)

What is causing the obesity epidemic?

We are overeating

Friedman Hypothesis

We eat because liver ATP levels are reduced below some threshold amount

Is there an Epidemic of Obesity

Yes