Pathophysiology of Obesity

Question 1

Give two good adipokines and their function. What are they released by?

Answer 1

Both release by white fat cells (large globs of fat)

1. Adiponectin - increase insulin sensitivity, decrease inflammation
2. Leptin - act on neurons in the arcuate nucleus of the hypothalamus to decrease food intake

Question 2

How do visceral and subcutaneous fat differ with respect to adipocyte size, inflammation, protective adipokines, and contribution to metabolic syndrome?

Answer 2

Visceral - large droplets, high in inflammation and low in protective adipokines, contributes greatly to DM and metabolic syndrome

SubQ fat - small droplets, low inflammation, good protective cytokines, do not contribute to DM and metabolic syndrome

Question 3

What is the definition of obesity by waist size?

Answer 3

Men: >40”
Women: >35”

Question 4

Why do we not see insane weight gain which is theoretically predicted with caloric excess over 30 years?

Answer 4

The BMR of the body is increased as more caories are consumed

• > food energy becomes less efficiently used
• > trained athletes usually have a lower BMR than coach potatoes

Question 5

What will destruction of VM hypothalamus cause and why?

Answer 5

Cause hyperphagia and obesity - since Ventromedial thalamus is the satiety center

Question 6

What will destruction of Lateral hypothalamus cause and why?

Answer 6

Aphagia-> anorexia and weight loss - since LH hypothalamus is the feeding center (motivation to eat)

Question 7

What are the neurons of the arcuate nucleus of the hypothalamus which are orexigenic? Are they stimulated or inhibited by leptin? Ghrelin?

Answer 7

NPY (neuropeptide Y) + AgRP (agouti related peptide) -> stimulate hunger (orexigenic)

These are inhibited by leptin
These are stimulated by Ghrelin

Question 8

What are the neurons of the arcuate nucleus of the hypothalamus which are anorexigenic? Are they stimulated or inhibited by leptin?

Answer 8

POMC and alpha-MSH -> inhibit hunger (anorexigenic)

These are stimulated by leptin
These are inhibited by ghrelin

Question 9

What is the function of ghrelin? What secretes it?

Answer 9

Secreted by fundus of stomach when the stomach is empty -> stimulates appetite

Decreased ghrelin levels when stomach is full

Question 10

What hormones secreted by the intestine / pancreas and inhibit appetite? How do they do so?

Answer 10

1. Peptide YY
2. GLP-1
3. Cholecytokinin
4. Amylin
5. Insulin

All stimulate POMC / MSH receptors in the arcuate nucleus

Question 11

What are the receptors for alpha-MSH in the arcuate nucleus? What happens when they are activated?

Answer 11

MC3 and MC4

When activated, like POMC neurons, the appetite is suppressed and the BMR is raised

Question 12

What happens to those with heterozygous MC4 mutations?

Answer 12

These mutations are found in up to 2.5% of people with BMI >30 -> indicate there is a problem suppressing appetite in obesity.

Question 13

What might MC3/MC4 agonists and antagonists be useful for?

Answer 13

Agonists - treatment of obesity

Antagonists - treatment of cachexia and anorexia

Question 14

What is the mechanism of action of orlistat and its clinical use? Side effect?

Answer 14

Inhibits gastric and pancreatic lipase -> decreased breakdown and absorption of dietary fatty acids

Use: Obesity for weight loss

Side effect: explosive steatorrhea pg. 383

Question 15

What drug acts as a 5-HT2C receptor agonist for weight loss? Mechanism of action after receptor binding?

Answer 15

Lorcaserin.

Stimulation of these receptors leads to POMC production -> satiety -> weight loss

Question 16

What is the most used gastric bypass procedure?

Answer 16

Roux-en-Y -> hook up cardia of the stomach to the small intestine.