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Is Eating Behavior really Controlled by a Biological Signal? (According to Doctor Levitsky)

Long story short, probably not because:
Eating Behavior is modulated by many neurochemicals.
These neurochemicals are not behaviorally specific
Biological Theories of Eating are based on concept of Homeostasis but there is ENERGETIC ERROR
Rise of Hedonics as a major cause of eating behavior.

What factors do you think cause obesity?

excess calorie consumption
inadequate energy expenditure
constant and excessive calorically dense food access

What does it mean to be obese? What is the difference between overweight and obesity?

obesity is excess amount of body fat
overweight is excess body weight for a particular height from fat, muscle, bone, water or a combination of these factors

How do we determine if one is obese? What are the strengths and weaknesses of this measure?

BMI (weight in kg over height in m squared)

strengths are that BMI is easy to calculate, reveals a general overview of body structure, and clearly shows weight to body load
weaknesses are that BMI does not distinguish between the many factors that cause weight (fat mass, bone mass, lean mass) or genetics

Why do we as a country care about obesity?

Expensive and shortens lifespan/healthspan
Obesity is either a risk factor or associated cause of death for many of the top causes of death

How is obesity a risk factor or associated with death? (describe its influence on organ systems)

low grade inflammation ~ DNA damage, cancer, Alzheimers
fat storage ~ NAFLD, cardiovascular disease, stroke, gallbladder disease

What is Dr. Berry's thoughts on dieting

All diets work to cause weight loss (restriction tips the balance to favor energy expenditure), BUT most diets are not manageable over long periods of time.

Compared to other animals, how do humans burn calories? What does this tendency lead to and why is this evolutionarily favorable?

Primates burn less energy/day than other mammals
Primates burn less energy/pound than other mammals

Conclusion: Species with greater energy expenditure per pound tend to grow faster, reproducemore, and die at earlier ages than those with lower expenditure per pound. Primates (includinghumans) burn much less energy each day than other mammals, whichcorresponds with primates' slow life history schedules and long lives.

Do humans differ from our Ape primate ancestors in energy balance? (calories in, calories out) What behavior is it that does/or does not contribute to this difference?

Humans combine social and foraging efforts, sharing surplus food energy with other members of their group. Sharing increases the energy available for all tasks including reproduction and maintenance, leading to longer lives, larger families, larger brains, and increased activity. Humans burn more energy each day than other apes to fuel these traits. Greater energy expenditure also favors directing extra calories to fat (far more than in other apes) to survive periods of energy shortage.

Our bodies are primed to store fat

Simply put, metabolism is?

The work your cells do!
metabolism = total energy expenditure, the combined work that your 37 trillion cells do

What is the difference between calorie and Calorie?

lowercase calorie is the amount of energy needed to raise 1 mL of water by one degree Celsius
uppercase Calorie is 1000 calories, or a kilocalorie

So, for example A cup of dry Cheerios has 100 calories, but General Mills actually means is 100 kcal or 100,000 calories.

About how much of our calories come from carbohydrates? What are the three common types of carbs? What happens to excess carbs?

About half of our calories consumed per day come from carbohydrates

three basic types are fibers, starch, and sugar

Sugar and starches are digested and either burned or stored as glycogen....also can be converted into fat once glycogen stores are filled

How much energy is in fat?

Every ounce of stored fat holds ~250 kcals of energy!

Why should we not eat more protein than necessary? How much, on average, is necessary?

Tissues and molecules breakdown daily and are converted to amino acids. They travel to the liver and get converted to ammonia then into urea and secreted.
• We clear ~50 grams of protein each day. Exercise increases this amount. We should only eat enough grams of protein to replenish this loss.

If we eat more than what we need—the protein is converted into amino acid -> ammonia, then urea, then excreted--this is now very expensive pee! (our bodies waste energy doing this conversion, plus bad for kidneys)

what is basal metabolic rate? How does body size influence BMR?

amount of energy body burns at rest (right when you wake up, haven't eaten)

pretty similar to basal energy expenditure, resting metabolic rate, and standard metabolic rate

The bigger you are, the bigger the organs and more cells, and as such more work needs to be done--higher BMR

Which organs contributes the most to Basal metabolic rate? Which organ contributes the least to BMR? What other organs contribute to BMR?

Brain is 60% of BMR

Fat is considered to have the lowest energy expenditure• Muscle, skin, and bone--make up the largest organs but are the quietest--muscle accounts for ~42% of body weight but only 16% of BMR -280 kcal/day--

Other organs include heart and liver

What factors influence energy expenditure?

• Basal metabolic rate (BMR)• Thermic effect of food (TEF) -• Activity= Total Energy expenditure

What is the respiratory exchange ratio (RER) and what does it tell us?

RATIO BETWEEN CO2 PRODUCED, AND OXYGEN USED
CAN BE USED TO CALCULATE RESPIRATORY QUOTIENT -FUEL METABOLISM
usually between 0.7 and 1.0, not too important

How long can a 250 Ib person survive a fast?

150 days

Have humans changed the number of calories burned per day? What study tested this and what was its method?

No, we have the same total energy expenditure as hunter-gatherers

Study was on Hadza hunter-gatherers which measured doubly labeled water (•Ingestion or injection of water labeled with isotopes of oxygen and hydrogen, which will be utilized in the body during metabolism.
•Difference in rates of disappearance of the two isotopes used to calculate the amount of CO2 produced in the body.)
of hunter-gatherers vs modern folks.

doubly labeled water

•Ingestion or injection of water labeled with isotopes of oxygen and hydrogen, which will be utilized in the body during metabolism.
•Difference in rates of disappearance of the two isotopes used to calculate the amount of CO2 produced in the body.

Does obesity influence BMR/ energy expenditure?

Nope. Even though you have more cells, the rate at which the cells work is the same

Can exercise change total energy expenditure? What evidence did we look at

There is an energy expenditure cap, where your body stops expending energy to fuel over-exercising
Only run for 20 minutes

How does exercise and over-exercise influence immune health

sedentary = high inflammation, normal WBC count
active = moderate inflammation, normal WBC count
extreme = low inflammation, low WBC leads to lymphopenia which causes low recovery and high risk of infection

Why do we need food/why do we eat?

Food provides...

• a source of energy to maintain our metabolic needs

• vitamins, nutrients, probiotics, minerals

• mode of socialization

• comfort

• happiness

What are the three components of metabolism? Describe them and their percent contribution to metabolism

Active Energy Expenditure (20%) = calories burned through activity, such as physical activity (intentional exercise) and NEAT (unintentional movement)

Thermic Effect of Food (10%) = calories burned through digestion and storage of food

Resting Metabolic Rate (70%) = calories burned at rest. A number of factors influence your RMR such as body size, age, gender, fat free mass, and fat mass

Why are nutrition labels based on 2000 calories a day?

Nutrition Labeling and Education Act of 1990
Extensive surveys done by USDA found men ate about 2000-3000 calories/day and women about 1600-2200 calories/day

How can metabolic rate be measured?

•Doubly Labeled Water Technique

Direct Calorimetry (Utilizing an enclosed system to measure the amount of heat that is produced from an individual)

What is the Mifflin-St. Jeor Equation?

a formula used to determine a person's RESTING metabolic rate (you multiply the number calculated from this equation by the proper PA factor)
•Men: (10 x weight) + (6.25 x height) - (5 x age) + 5
•Women: (10 x weight) + (6.25 x height) - (5 x age) - 161

What are some factors that influence RMR?

LBM (lean body mass)
height
age
hormones
stress
sex steroids
pregnancy/lactation

If an individual was once overweight (but now lost the weight), what happens to their calorie maintenance?

If an individual who was overweight lost weight, he/she would need to consume fewer calories than that of an individual who is the same body weight (never overweight) to maintain the current weight they are at...•
This is approximately 20% less calories than what they originally needed

What were the findings of the Minnesota Starvation experiment?

this experiment tested the effects of severe hunger on human psychology and physiology, demonstrating our tendency to focus only on food when hungry and our body's tendency to stay near its set point

The men lost weight rapidly, but after a certain point maintained the same body weight

The men primarily lost weight in the form of fat and tissue, but gained water weight

What are Factors that may contribute to energy dysregulation?

Genetics
Social + Economic Factors
Environment
High Intake
Low Expenditure

What are social + economic factors that contribute to energy dysregulation?

•Income gaps and social class cause Limited access to certain foods (more likely nutritious)

•Disadvantaged social status can lead to chronic stress which can cause physiological changes •Stress can also be associated with emotional eating thus increased energy consumption/intake

Weight Bias + Stigma•Modern day ideologies on the "ideal body type" can further induce stress

How do environmental factors contribute to increased food intake?

•Food accessibility•Increased portion sizes•High availability/convenience of food•Western diet and highly processed foods•Higher caloric intake associated with more processed foods than when compared with unprocessed ones•Increased sedentary lifestyle•Lower levels of sleep

How can/do we regulate our body weight?

Dieting, Optimal Exercise Activity

What percentage of weight loss is attributable to dieting and exercise?

Dieting Accounts for 70% of weight loss while exercise only accounts for 30%

All calories are the same, but not every calorie is created equally. What does this mean?

Calorie is a unit of measurement but highly processed food vs unprocessed food may provide differences in satiety

In terms of optimal physical activity for weight loss, what is the difference between high intensity vs low-medium intensity exercise?

at high intensity exercise, our primary fuel of energy is carbohydrates

Longer duration, low-medium intensity exercise is more effective in burning fat

How do you calculate your target heart rate zone for burning fat?

To determine target heart rate zone subtract your age from 220• Fat burning zone is between 50-70% of maximum heart rate

What can cause an increase in obesity prevalence: energy intake or energy expenditure?

energy intake

Compared to the 1970s, on average we eat how many more calories per day? This is associated with how much weight gain? (Also, How many calories stored in a pound of fat?)

400-600 calorie increase ~ extra slice of cheesecake
• 3,500 calories in a pound of fat• extra 400 calories per day• Every 8.75 days a new pound of fat would be added• 365 days/year• 41.71 pounds of fat/annum

How many calories are stored in apound of fat?

3500

Briefly describe how the natural environment influences weight?

• Food availability• Adaptation to food type and amount• Physical excursion• Temperature

In nature,can we observe obesity?

not really EXCEPT for "The spiny, venomous lionfish can kill three-quarters of a reef's fish population in just five weeks, according to one study." which leads to Intestinal fat deposits• Liver damage

Describe how Pima Native Americans are a good population to study environment driven obesity

• Reside in the American southwest and Northern Mexico
• Agriculture based society
• Eat a low-fat diet
• But trend towards having a higher BMI compared to other agriculture societies
THEY ARE ISOGENIC

Arizona Pima's became obese but Northern Mexican Pima's did not

What do twin studies tell us about obesity?

• Correlation of adoptee's BMI to biological parents not adoptive parents• Independent of environment

Genetic factors influence BMI

Why did the prevalence of rickets steeply decline? What is causing a slow rise now?

declined after vitamin D and calcium fortification of milk

there is a rise in rickets now because people switched to milk alternatives, which at one point were not fortified. now these milk alternatives are fortified. also juices are fortified.

Do nutrients play a role in obesity?

Maybe. Overweight/obese people have higher incidence of nutritional inadequacy than lean people in terms of Vit A, Vit C, Vit D, Vit E, Calcium and Magnesium

What percentage of variation in obesity is genetic?

~65%

What are the four general classes of genes associated with obesity? What is the specific gene that overlaps in all four classes?

Mono-genic obesity genes
Fat distribution genes
Overweight/ obesity genes
BMI gene

The MC4R gene overlaps in all four

What does melanocortin 4 receptor have to do with obesity? What is the prevalence of its deficiency?

MC4R gene is associated with obesity

Melanocortin 4 receptor deficiency occurs in about 1 per 1,000 people, making it commoner thanother high-profile genetic diseases such as Duchenne musculardystrophy or cystic fibrosis.

What is the thrifty gene hypothesis?

The hypothesis that since our ancestors lived in a time when food supply was unpredictable, natural selection favored individuals who stored more fat. In this hypothesis, fat storage was an asset, not a defect

Evolutionary selection of genes that favor obesity

What are some arguments against thrify gene hypothesis?

If true, modern humans in a food rich environment would become obese. More people than are obese, should be obese

Not enough evolutionary time for natural selection of obese inducing genes
Famines are infrequent and only have occurred since civilization (12,000 yrs)
Reproduction is low during famines or food scarcity (high mortality and low birth rates)
Why would obesity genes, knowing that it causes metabolic disorders, be beneficial?

Are famines a strong enough selection? What did the Dutch Hunger winter tell us?

1944-45 World War II German imposed food embargo on the Netherlands• After the embargo: researchers examined offspring conceived during this period

Offspring conceived during this famine had increased likelihood of obesity, type 2 diabetes and early mortality• 10% increase in mortality by 68 years old
Found changes in methylation statuses (epigenetic regulation) of starvation genes involved in metabolism

Basically when conceived, these babies thought they would be born into an environment with limited food, so their bodies were primed from conception to store fat. However, 9 months later, the famine ended, and there was adequate food, so these individuals stored more fat than others conceived during times of plenty.

How can obesity be inherited? Give an example supporting the idea that obesity is inheritable

Epigenetic regulation
An intersection between the environment and genetics

An example is that adopted children have BMIs that resemble their biological parents, not their adoptive parents

What is epigenetic regulation?

oDNA is wrapped around histones
oDNA transcription is regulated by how closely histones are packaged (closer oEpigenetic marks such as DNA methylation influence the transcription potential of genomic regions and once changed, can result in long-term effects
oHence, the central dogma of biology, with a linear flow of DNA / RNA / protein, is overly simplistic. Gene and protein expression is regulated by several layers of epigenetic mechanisms, resulting in an intricate combination of chromatin accessibility and transcription factor recruitment to coding sequences

What is the Example of an obesity inducing SNP we learned about?

FTO
• Fat mass and obesity associated gene (FTO)• FTO demethylates RNA• Changing the methylation status on mRNA alters the amount of protein made

• Dysregulates genes involved in energy metabolism and adipose tissue homeostasis -adaptive thermogenesis?

What percentage of type 2 diabetes can be attributed to genetic heritability?

Only about 5-10% of type 2 diabetes can be attributed to genetic heritability

assortive mating for obesity

obese people pair up and reproduce obese children

What can we taste?

Bitter (natural toxins)
Sweet (energy rich)
Sour (acids)
Umami (amino acids, meat, cheese)
Salty (electrolyte balance)

3 main cell types of taste buds

◦Dark Cells (Type I)
◦Light Cells (Type II)
◦Intermediate Cells (Type III)

Type II cells sense taste stimuli and type III cells transmit taste signals to sensory afferent nerve fibers. However, type I cells are not considered to possess obvious taste functions.

How often are taste receptors rejuvenated?

every ten days via stem cells

What receptors are activated by sweet tasting things?

T1R2 T1R3 is activated by a diverse set of stimuli including carbohydrates (mono- and disaccharides), sugar alcohols, sweet peptides and proteins, and other small molecule sweeteners

Do we think obesity induceschanges in dopamine altering food perception and eating behavior?

Obesity reduces dopamine receptors and dopamine release

Obese people have to eat more food (or more sweetness/saltiness) in order to release the same amount of dopamine as a lean person

Do obese humans perceive taste differently?

Yes, when it comes to saltiness specifically the signal strength is lower, and the sensation is short lived.

Four main taste circuits disrupted in obesity

1. reward-saliency

2. motivation-drive

3. learning-conditioning

4. inhibitory control-emotional regulation-executive function

Mayer Glucostatic theory. What is it? What evidence supports it?

The theory: Changes in glucose regulate appetite and feeding behavior

Supported by:
lean, obese, and diabetic people eat a meal.
measure blood glucose after meal (Measured arteriole and venous glucose)
measure when participants crave more food/eat again
The findings are that a decline in blood glucose levels influences appetiteParticularly when arteriole and venous blood glucose levels reach equilibriumArgues that inadequate delivery of glucose to the brain ('neuroglucopenia' or 'glucoprivation') activates the neurocircuits that drive feeding along with wide-ranging neuroendocrine and autonomic responses

Lower Dips in glucose are associated with hunger and energy intakein HEALTHY INDIVIDUALS!

How does stevia taste compared to sugar?

Stevia is 300 times sweeter than sugar. You can use less!

Can artificial sugars change blood glucose levels? Can artificial sugars increase our risk for T2D?

No conclusions; mixed results show that there is a positive association, negative association and no association between artificial sweeteners and blood glucose/insulin levels.

What did the Dando et al study on mice fed a HFD diet show? Why might this effect have happened?

Mice were fed a HFD for 8 weeks and taste bud abundance was measured. There are fewer taste buds in obese mice.
Why?
-Less taste receptor stem cell proliferation (taste receptors are rejuvinated every 10 days via stem cells, but stem cells proliferate less in response to HFD)
-More cell death
-Related to HFD induced inflammation

What does a sweet taste receptor do in the gut? (in other words, how do sweet taste receptors react after being activated?)

Sweet taste receptors are located on enteroendocrine cells of the gut.
Senses sweet substances and causes the release of Glucagon-Like-Peptide 1 (GLP-1).
GLP-1 targets the neighboring enterocytes to stimulate glucose uptake from the intestines.
GLP-1 then targets pancreatic beta cells to secrete insulin in response to sweet substances.

What taste is associated with CCK? What is the function of CCK? (Cholecystokinin)

When bitter taste receptors, located on enteroendocrine cells, are activated they release CCK CCK has two actions:

1. Activates the CCK-Receptor located on enterocytes that activate pump transporters that remove toxins for the enterocyte and moves it back into the intestinal track.

2. Activates CCK-Receptors located along the vagus nerve which sends a signal back to the brain to stop eating CCK stops food intake and depends on the CCK-Receptor

What makes ghrelin special?

Ghrelin is the only orexigenic peptide hormone known to be produced in peripheral organs

How does ghrelin work? What does ghrelin change in response to and how does it induce behavioral changes? What hormone is ghrelin associated with?

2 Modes of action regulating food intake

1. Circulation and hypothalamic regulation

2. Vagal nerve stimulation within the gut

ghrelin changes in response to feeding and fasting. after being fed, ghrelin levels are low but when fasted, ghrelin levels are high Intracerebroventricular injection of Ghrelin increases weight and promotes hyperphagia Ghrelin alters respiratory quotient but not TEE! -> (ghrelin doesn't change energy expenditure, but just changes the things you digest)

Ghrelin stimulates growth hormone release

Is ghrelin alterned in obesity?

ghrelin levels are decreased in obesity
Obesity is associated with elevated insulin and leptin levels which have been shown to disrupt Ghrelin production (leptin is released by adipose tissue)

Loss of Ghrelin reduces Growth Hormone in obese individuals which could be negative feedback onto
Ghrelin regulation
Physiological adaptions to a positive energy balance associated with obesity could reduce Ghrelin levels

Where in the gut is Ghrelin synthesized?

Enteroendocrine cells within the stomachPost-translationally modified to be secreted

GOAT (Ghrelin O-acyl-transferase)

Essential for ghrelin acylation - this form of Ghrelin is thought to control food intakeThe GOAT enzyme acts a nutrient sensorIn response to fatty acids GOAT becomes activated and modifies GhrelinGOAT uses dietary lipids as substrates for ghrelin acylation

How does circulating ghrelin work?

1. Crosses blood brain barrier

2. Binds to neurons of the median eminence

3. GHS-R1a (ghrelin receptor) is activated in ARC, VMH and PVN neurons.

4. ARC contains orexigenic neurons: NYP/AgRP.

5. Ghrelin induces food intake by potently activating NPY/AgRP neurons

How does vagal nerve suppression ghrelin work?

1. The vagus nerve afferent nerve endings penetrate the gastrointestinal mucosa and connect with enteroendocrine cells

2. GSH-R1 is present on vagal afferent nerve

3. Ghrelin binds to GHS-R1a and suppresses electric activity of the vagal nerve

4. This electrical signal reaches the NTS where the signals are transferred to ARC neurons to stimulate food intake

What is the status of ghrelin mimetics as therapeutic weight loss targets?

many proposed drugs are either inactive or being studied.

Age-related weight gain is the best predictor of what diseases? How many more calories per day is associated with age-related weight gain?

Obesity, Diabetes, Atherosclerosis (Heart Disease, Stroke), Colon Cancer
10-25kcal/day

What is Levitsky's Law?

∆ Weight = ∆ Calorie In - Calorie Out
But the problem about the rise in obesity rates over time isn't that we're expending fewer calories, we just consume more calories than ever before.
Remember that people in the past (hunter-gatherers) worked more than us, but also rested a lot more, so overall our metabolisms are the same.

What is Energetic error? What eating behaviors are associated with this error?

Eating Behavior is not homeostatic. If you eat too much at one meal, you often don't compensate by eating less at the next meal (or vice versa)
Alternate Day Fasting, Exercise, Meal Skipping, Substitutes and Underfeeding behaviors -> people do not compensate. They end up in a caloric deficit
Composition (fatty, sugary), overfeeding, portion -> people do not compensate. They end up in a caloric surplus.

What was Levitsky's Freshman 15 study? What other studies arose after this?

Weighed freshman over a few semesters to see if it is true that freshman gain about 15 ibs -> they don't gain exactly 15 ibs, but they do gain weight.

Levitsky separated freshman into groups. Control group continued their normal behavior, while experimental group weighed themselves every morning.

Control group gained weight. Experimental either lost or maintained weight (depending on the year).

Levitsky also did the two year study of cornell wellness center (health-conscious older), and cornell staff (older) and found similar results

What is the hypothesis behind why weighing yourself every morning works to maintain or lose weight? How did Levitsky test this hypothesis?

Reduces the effects of food primes that make us consume a little more energy than we expend.

Levitsky tested groups by measuring how much food was consumed while they watched either positive food primes (a Burger King commercial), or negative food primes (a car commercial) (or an exercise video).
positive food prime -> eat more
negative food prime/exercise vids -> eat less

Then, Levitsky tested whether having participants step on a scale before having them watch a positive food prime video -> when weighed before watching a food-related video, you eat less food.

Also, when discussing health vs discussing careers, you eat less food when discussing health

priming theory of age related weight gain

age related weight gain is exacerbated by imprecise energy compensation and food priming

imprecise energy compensation -> Even if not hungry, people will eat if food is presented
food priming -> we live in an obesogenic environment (commercials, stores...)

How does priming cause overeating?

1. Seeing food (commercials)

2. Portion Size (portion size is increasing)

3. Variety (buffets, restaurant menus...)

4. Social Facilitation (going out to eat; we eat out more often than ever and there are more restaurants than ever).

What is one of the largest changes in eating behavior between 1987-present discussed by Dr. Levitsky?

money spent on foods eaten away from home has exceeded money spent on foods eaten in the home. (both have increased though).

What do we know about eating at a restaurantcompared to eating at home?

1. Fat Content of food is higher

2. Portions sizes are larger

3. Eating with more people

4. Variety of foods is greater

5. More advertisements