Obesity and Regulation of Appetite

Question 1

What BMI increases the risk of death from CV disease and cancer in men and women?

Answer 1

Underweight (less than 18.5)

and overweight (25-29.9), obese (30-34.9), obesity II (35-39.9) and extreme obesity (40+)

Question 2

What waist circumference places one at an increased risk of CV related disease?

Answer 2

Men: 40+ in

Women: 35+ in

Question 3

Does obesity have a genetic component?

Answer 3

Yes, twin studies show 50% concordance of obesity

Question 4

While obesity is typically a very polygenic disease that incorporates both risk factors and genetics, it can be caused by monogenic conditions. What are some rare (less than 5%) monogenic causes of obesity?

Answer 4

Melanocortin-4-receptor mutations

Leptin or leptin receptor deficiency

POMC gene mutations

Prohormone convertase-1 mutations

PPARy2 mutations

Thyroid hormone receptor-B mutations

Question 5

What are some substances that promote weight gain?

Answer 5

Melanin-concentrating hormone

Agouti-related peptide

Neuropeptide Y

Androgens

Progesterone

Endocannabinoids

Somatostatin

NEED GOGO

Question 6

Other things that promote weight gain?

Answer 6

Nor

Epi

B-Endorphin

Dynorphin

Ghrelin

Opiods

Galanin

Orexin A and B

Question 7

What are some substances that promote weight loss?

Answer 7

GLP-1

Urocortin

Neurotensin

Serotonin

Bombesin

a-Melanocyte-stimulating hormone

Dopamine

GUNS BAD

Question 8

Other weight loss promoting drugs?

Answer 8

Leptin (made in fat)

Insulin (inhibits appetite)

Peptide YY3-36

Enterostatin

Corticotropin-releasing hormone (CRH)

Cocaine-amphetamine-regulated peptide (CART)

Ciliary neurotrophic factor

Cholecystokinin

LIPE CCCC

Question 9

What is the endocannabinoid system?

Answer 9

An endogenous signaling system that consists of two types of receptors, CB1 and CB2, and several endogenous compounds, including anandamide and is generally silent, but becomes activated to reduce pain and anxiety, inhibit motor behavior, induce appetite, extinguish aversive memories, and modulate body temp, hormone release, and smooth muscle tone

Question 10

How does Pentermine work for obesity treatment?

Answer 10

It stimulates nor release

Question 11

How does Dexfenfluramine work for obesity treatment?

Answer 11

It increases the release of serotonin

Question 12

How does Fenfluramine work for obesity treatment?

Answer 12

It decreases uptake of serotonin uptake

Question 13

How does Lorcaserin work for obesity treatment?

Answer 13

It is a 5HT2c receptor agonist

Question 14

How does Sibutramine work for obesity treatment?

Answer 14

It blocks nor, serotonin, and dopamine reuptake

Question 15

How does Rimonabant work for obesity treatment?

Answer 15

It is a cannabinoid receptor inhibitor

Question 16

How does Liraglutide work for obesity treatment?

Answer 16

It is a GLP-1 analog

Question 17

What does orlistat do?

Answer 17

Inhibits lipase action in the GI to treat obesity

Question 18

Does modest weight loss (5-10%) help at all in obese pts with HTN, type II diabetes, or dyslipidemia?

Answer 18

Yes, it results in:

–Improved diabetes control (remission ~16%)

–Improved blood pressure control

–Improved lipid profile

–Need for fewer medications

Question 19

How does leptin work?

Answer 19

Leptin is secreted by the fat cells and is the peripheral arm that tells the satiety center (arcuate nucleus) how much energy is in the body and causes secretion of POMC and CART, which inhibit appetite via causing a-MSH to be expressed and bind to MC4R in the hypothalamus to cause secretion of anorexigenic effectors such as CRH and TRH and inhibit orexigenic effectors such as MCH and orexin

Question 20

Note about fecal transplants

Answer 20

There is accumulating evidence that fecal transplants from thin mice into obese mice can reverse signs of obesity

Question 21

What are some co-morbidities associated with obesity?

Answer 21

diabetes

sleep apnea

cancer

decreased fertility

HTN, CVD, stroke

Question 22

Describe the pathopshyi of obesity leading to heart failure?

Answer 22

Increased caloric intake causes increased thyroid hormone production, leading to increased sympathetic tone and metabolic rate, which causes increased CO and eventually HF

similarly, increased visceral fat storage leads to increased free fatty acids and insulin resistance which leads to hyperinsulinemia, leading to increased sympathetic tone, and then increased BMR, CO, leading to HF

Question 23

How does increased sympathetic tone lead to HTN?

Answer 23

again increased caloric intake can cause increased thyroid hormone secretion leading to increased sympathetic tone which:

causes vasoconstriction, increased CO, and increased Na+ resorption from the kidneys all leading to HTN AND

hyperinsulinemia leads to vascular smooth muscle hypertrophy

Question 24

How would obesity lead to gallstones?

Answer 24

obesity increased estrogen which increased cholesterol turnover/excretion leading to risk of gallstones (and cancer)

Question 25

Which bariatric surgery results in the greatest initial wgt. loss?

Answer 25

Biliopancreatic diversion (39%)

followed by:

Roux-en-y gastric bypass (34.9%)

Gastroplasty (24.3%)

Question 26

Mortality Benefit of Bariatric Surgery?

Answer 26

• 10.9-yr SOS Study cohort: 30% risk reduction for overall mortality in 2,010 obese patients following surgery vs. community control.
• Retrospective cohort (N= 7,925): mortality from any cause was 40% lower than in 7,925 nonsurgical obese patients.
• Propensity-matched VA study: No decreased mortality from surgery (vs. usual care) during a mean 6.7 yr of follow-up.

Question 27

AEs of bariatric surgery?

Answer 27

micronutrient deficits, hypoglycemia, and waning effects