Review for Obesity Exam 1

What are some deleterious health outcomes from obesity?

CV disease, diabetes, stroke, cancer, mental health like depression, ..

• What is the equation to calculate BMI?
Include the units of measurement in both the numerator and denominator.

Kg/meter‐squared

This BMI calculation applies to
a. Men
b. Women
c. Adults, but not children
d. Both adults and children

d. Both adults and children

What are the BMI ranges for ‘healthy,’ overweight, and obese classifications?

About 18.5‐24.9, healthy
• 25‐29.9, overweight
• 30 and up, obese
• Grade II and II in 5‐point increments above
that

What is the approximate percent of US adults in each category?

• About ~<30%, >30%, and 42%

Name a factor (something that differs between people, like demographic) that changes obesity rate

Nationality, age, sex/gender, race, ethnicity, SES, education, geographic location

DXA is a measure of….

Body composition

Calorimetry/respirometry is a measure of…

Energy Expenditure

Water or air displacement…

body composition

Doubled-labeled water is a measure of…

Energy Expenditure

Accelerometry or step counts

Physical Activity

What is one plus and one minus about the use of BMI as a metric for obesity?

Plus: easy, data are collected routinely, factors out
most of bias according to things like sex and height,
not yet identified an index that is better
• Minus: not that great at predicting fat percent—
underestimates o/w and obesity; some bias with tall
folks, and with race (overestimate risk in Af‐Amer,
underestimate in As‐Am)

What is the difference between visceral and subcutaneous fat

Health risk worse with visceral—around
organs
• Tend to be a sex difference

How or why is excess body fat unhealthy?

• 1—portal/visceral hypothesis
• 2—fat load, including secreted factors
• 3—fat infiltration into organs (ectopic fat)
• 4—inflammation
• Also 5—load burden (e.g., disability)

In food‐recall diaries, how accurate is the amount (kcal) intake reporting?

• Underreport for self‐report

What are some factors that increase or decrease accuracy?

Underreport more in those with obesity, or if food is considered ‘bad’

What happens to habitual kcal intake when people record kcal as they eat?

Goes down—take it as an opportunity to diet, plus constant recording is kind of a pain

Define the ‘obesity paradox,’ and tell me one possible reason for this statistical, epidemiological effect.

Statistical phenomenon where BMI (and health variables that go along with it) do not correlate with survival or all‐cause mortality—overweight and mild obesity BMIs are relatively protective, statistically speaking

• Reason: actually measuring lean mass, not fat/obesity, with BMI, in these cases; indirectly indicating decline because of disease process

What is one factor that differs between ‘metabolically healthy obesity’ and unhealthy obesity? (health parameter)

Lipids, CV risk

What is one health‐related effect that does not differ?

disability

Where is leptin secreted from and does it increase or decrease appetite?

Leptin –white fat, decrease appetite

Where is Ghrelin secreted from and does it increase or decrease appetite?

stomach, increase appetite

Where is GLP-1 secreted from and does it increase or decrease appetite?

gut (intestine), decrease appetite

Where is Insulin secreted from and does it increase or decrease appetite?

beta islet cells of pancreas, decrease appetite

What is the name of the hypothalamic nucleus at the base of the brain where these hormones act on two specific sets of cells— ‘orexigenic’ and ‘anorexigenic’?

Arcuate

What peptides or precursors are contained in the ‘orexigenic’ cells?

AgRP, NPY, GABA

What about the ‘anorexigenic’ cells?

POMC (cleaves into aMSH ad others) and CART

Name one brain region where these neurons project.

PVN, VMH, DMH, lateral hypothalamus
– Those are all hypothalamus
• Hindbrain (NTS)

Name one hindbrain region that is important in the modulation of energy balance.

• AP—area postrema
• NTS—nucleus of the solitary tract
• DMV—dorsal motor nucleus of vagus

What does Cannabinoids do to your appetite?

Increase appetite

What does aMSH do to your appetite?

decrease appetite

What does Orexin do to your appetite?

increase appetite

What does Leptin do to your appetite?

decrease appetite

What does Ghrelin do to your appetite?

Increase appetite

The mesolimbic reward pathway starts in the midbrain nucleus:

ventral tegmental n (VTN)

Cells in this area make and release DA into this forebrain region of the limbic system:

Nucleus accumbens

onus: what is another region that is a recipient of these DAergic projections?

Prefrontal cortex, insula,

In the incentive salience theory, with repeated stimulation, the salience of the cues and ability of cues to increase drug seeking, or ________, increases because of sensitization...

wanting

whereas the hedonic value of the rewarding stimulus, or the _______, decreases because of tolerance.

liking

What could you change to increase liking or wanting alter your likelihood of overeating?

Some genetic, high exposure to palatable food in diet, obesity, reward substitution, maternal exposure (mom’s fault)

What could you change to decrease liking or wanting alter your likelihood of overeating?

change diet (decrease energy density)

What stimulates/activates Sirtuins?

calorie restriction, resveratrol

What stimulates/activates AMPK?

AMP:ADP ration, ‘fuel gauge’

What stimulates/activates mTOR?

–protein/amino acid, rapamycin, insulin, growth factors

What stimulates/activates PPAR?

nuclear receptor for FFA

What stimulates/activates PGC1a?

‘master regulator,’ cofactor for PPAR

If you overfeed a lab rodent while they are gestating pups, then raise the pups to
adulthood, what is their likely phenotype?
• Weight, body composition
• Food intake
• Food preference

–Higher weight, adiposity

–Higher

–prefer energy‐dense, high‐fat foods

Name some things that can change or underlie differences in the brain reward response to food, for example palatable food.

Genes
• Maternal programming
• Diet exposure
• Obesity

Briefly define these methodologies or strategies used to measure the genetic contribution to obesity:
• Linkage analysis …..

What chromosome regions nearby each other are inherited along with obesity

Briefly define these methodologies or strategies used to measure the genetic contribution to obesity:

Candidate gene approach……

–ID candidate genes from protein faction in the cell

Briefly define these methodologies or strategies used to measure the genetic contribution to obesity:

GWAS….

genome‐wide association, sequence a lot of
genes in a lot of people then see what is significant, then determine function

Briefly define these methodologies or strategies used to measure the genetic contribution to obesity:

Twin studies…

–heritability between monozygotic vs dizygotic twins

Name a gene variant that is commonly identified in GWAS studies:

FTO, MC4R

About what is the increased risk of obesity, or extra BMI or kg incurred, with the risk variant?

A few kg for FTO, as low as a few grams for many others

Name one gene or system impacted in a monogenically‐caused obesity.

Leptin‐melanocortin
• (leptin or its receptor, POMC or cleavage enzymes, melanocortin receptors especially
MC4R, downstream mediator BDNF & its receptor)

What is the heritability of obesity? In other words, how much of your obesity risk is attributable to your parents?

~50‐60‐ish %, depending on BMI (higher for high BMI, lower for low BMI)

About what percent of obesity risk is accounted for by monogenic causes?

Maybe 5%

What about the total of all the common and uncommon gene variants?

Maybe 40%

What might explain the gap between heritability & genes’ contribution?

“missing heritability”—epigenetics/maternal programming, interactions between variants, complex interaction with environment

With relationships, what will statistically increase your chances of developing obesity— having a neighbor who is obese, or a best friend who is obese?

FRIEND

How does undernutrition during pregnancy impact offspring health as an adult?

Which trimester(s) matter the most?

Increase risk of metabolic disease

First half

How does gestational overnutrition impact offspring health?

What are some mechanisms for this?

increase risk of metabolic & CV disease

Gestational inflammation, placental permeability, neurogenesis, epigenetics

What is one risk of maternal obesity?

Gestational diabetes, macrosomia (very big baby)

What happens if you induce weight loss in the mom, then have more offspring—how does that change the risk for the new babies?

Can partly reverse effects

You induce stress in a lab rodent while she is gestating pups. Then you let the pups grown up. How is their energy balance changed?
What about the offspring stress response?

Higher adiposity
• More responsive to stress
• (Might vary depending on the sex of the
offspring)

What about the US diet has changed in the last 50‐100 years?

Higher portion size, maybe higher fat content (conflicting info on that), cheaper, dine out more often, more availability and variety of palatable foods

What has changed about physical activity in the past 100‐150 years?

Lower daily activity

Which is the most energy‐dense macronutrient (kcal/g)?

Fat, at 9 kcal/g
• Alcohol is 7 kcal/g
• Carb and protein are about 4 kcal/g

If you are on a diet, which macronutrient(s) should you be sure are high or low to ensure the best results?

–a. Fat
–b. Carb
–c. Protein
–d. Whichever you can stick to long term

– Whichever you can stick to long term

Macronutrient composition matters because:
– GI can affect insulin sensitivity
– Protein might affect satiety, but the jury is still out
– Dietary fat may affect the brain reward system
– Some macronutrients cause food addiction

-GI can affect insulin sensitivity
– Protein might affect satiety, but the jury is still out
– Dietary fat may affect the brain reward system

What personality traits are more or less likely to be associated with weight gain or obesity?

Impulsivity, sensitivity to reward (more)
• Persistence (less)

Total daily energy expenditure can be divided up into (define these and say what percent of daily EE each accounts for):
• BMR
• TEF
• Activity EE

-BMR ~60%
• TEF ~10%
• Activity EE ~30%

What is the predominant determinant(s) of BMR?

Body size, especially lean or fat‐free mass

What is the predominant determinant(s) of TEF?

Amount of food eaten, food type & macronutrient composition to some extent

What is the predominant determinant(s) of Activity thermogenesis?

amount of activity, and size/load

What happens to EE if you are in negative energy balance and lose weight?
• Why?
• What about overeating?

-Decreases

-Less mass to support, adaptive thermogenesis

-Some increases in EE

True or false: “Vanilla” obesity is usually due to a large deficit in daily energy expenditure or metabolic rate.

FALSE

Name a job of white adipose tissue

Store fat, insulate, immune role, adipokines

What activates lipolysis in WAT?

SNS, some hormones (like glucagon)

What is the primary job of brown fat?

Thermogenesis

What activates this process?

SNS, beta adrenergic, UCP

What can cause ‘browning’ of white adipose tissue (WAT)?

– Calorie restriction
– Exercise
– Environmental enrichment (in critters)
– SNS
– At the level of the cell, cellular inducers like
PRDM16

How does reproduction affect metabolism in:
– Sex differences?

Different fat storage, E effects on fat and brain

How does reproduction affect metabolism in:

Changes over the estrous cycle?

hormone effects on activity and appetite

How does reproduction affect metabolism in:

Puberty?

Change fat distribution

How does reproduction affect metabolism in:

Pregnancy?

Fat distribution, energy allocation (insulin sensitivity), increase EE

How does reproduction affect metabolism in:

Photoperiod or seasonal cycles?

Change appetite and fat storage, lipolysis/lipogenesis

How does negative energy balance affect reproduction? Give an example.

Can suppress puberty, or block cycle—either decrease food intake or a lot of exercise
• Impact motivation as well as probability of ovulating

The nucleus of the hypothalamus contains cell populations that are "orexigenic" and "anorexigenic," responding to homeostatic cues like hormones, and other cues.

a. Paraventricular (PVN)

b. Arcuate (ARC)

c. Ventromedial (VMH)

d. Leptin

b. Arcuate (ARC)

In the orexigenic and non-orexigenic cells described above, name one peptide (or precursor, or neurotransmitter-NOT a hormone) contained in these cells, and tell me which cell (orexigenic or non-orexigenic) uses this peptide _______

Is it "orexigenic" and "anorexigenic”?

Eg:

CART

anorexigenic

Endocannabinoids act on CB1 receptors in the brain to affect appetite. Does it/increase or decrease appetite?

increase

Name one other aspect of behavior or physiology that is also changed (related to appetite or not, either is fine):

decrease in EE

Which one of these hormones is a gut hormone that acts on receptors in the brain to increase hunger?
a. Ghrelin
b. CCK (cholecystokinin)

c. GLP-1

d. Insulin

e. Leptin

a. Ghrelin

Which one of these hormones is a gut hormone that acts on receptors in the brain to decrease hunger and also is an incretin which amplifies insulin release from pancreatic beta cells?

a. Ghrelin

b. Insulin

c. CCK (cholecystokinin

d. Leptin

e. GLP-1

e. GLP-1

Which of the following intracellular energetic signaling molecules senses changes in ATP consumption, production, and/or demand through sensing changes in the ATP/AMP ratio?

a. Sirtuins

b. AMPK

c. mTOR

d. Leptin

b. AMPK

As a population parameter, about how much of BMI is inherited (heritable)?

a. 2-5%
b. 10%
c. All of it- nearly 100%

d. As a whole, about 40-50%, but it matters more at higher BMIs (60-80%) than lower BMIs (30-35%).

d. As a whole, about 40-50%, but it matters more at higher BMIs (60-80%) than lower BMIs (30-35%).

About how much of adult severe obesity (as a percent) is due to monogenic causes (i.e., a mutation in one gene that causes the person to be obese)?
a. 5%, give or take

b. 45-50%

C. 70%, to match the ~0.70 heritability of obesity or body weight

d. Close to 100%

a. 5%, give or take

What is BMI?
A. Stands for body motion index
B. Weight (in lbs) over height (feet & inches)
C. Used to categorize population overweight &obesity
D. Considered a valid estimate of individual body fat

C. Used to categorize population overweight & obesity

How does increased lipid accumulation lead to
deleterious health outcomes?
A. Lipid overflow & ectopic fat where lipids interfere with cellular function
B. Adipose tissue also secretes pro‐ inflammatory factors
C. Visceral fat can lead to higher portal lipid levels, which can harm liver insulin sensitivity
D. All of the above are reasons why excess fat accumulation can be harmful

D. All of the above are reasons why excess fat accumulation can be harmful

What is true about BMI?
A. Gives an accurate estimate of body fat irrespective of sex, age, or height
B. Can give a skewed view of health risk depending on sex or ethnicity
C. An overweight or obese BMI category overestimated the health risk

B. Can give a skewed view of health risk depending on sex or ethnicity