Obesity and regulation of appetite: Nyenwe

Question 1

Recall the factors contributing to energy balance and weight control.

Answer 1

A few rare monogenic causes of obesity:
Melanocortin-4 receptor mutations
Leptin deficiency
Leptin receptor deficiency
POMC gene mutations
Prohormone convertase-1 mutations
PPARgamma2 mutations
Thyroid hormone receptor-B mutations

Mostly: energy intake&raquo_space;> energy expenditure

Substances that promote weight gain:
Neuropeptide Y
Melanin-concentrating hormone
Agouti related peptide
Ghrelin
Orexin A and B
NE and Epi
Opioids
Endocannabinoids (weed)

Substances that promote weight loss:
Leptin
Peptide YY
Insulin (appetite suppression)
Glucagon-like peptide 1 (GLP-1)
Cholecystokinin
a-melanocyte stimulating hormone
Cocaine-amphetamine regulated peptide
Serotonin
Dopamine

Question 2

Become familiar with central and peripheral signals that regulate appetite, food intake, and energy balance.

Answer 2

Appetite center of brain: Arcuate nucleus –> PVN
::Leptin —I agouti related peptide that normally —I MC4 receptor that is anorexigenic and —I orexigenic (appetite stimulating) repectors.
::Leptin —> melanocyte stimulating hormone —> MC4 receptor that has above described effects.

• BIG PICTURE: Leptin, GLP-1 inhibit appetite!*
• Agouti-related peptide, ghrelin stimulate appetite*

Question 3

Understand the role of obesity in the pathophysiology of disease.

Answer 3

Comorbidities of obesity:
T2DM
Cancer
Psychosocial issues
HTN, CVD, stroke
v fertility
DJD, rheum
gallstones
sleep apnea

Question 4

Outline the approach to management of obesity.

Answer 4

Lifestyle modification:
exercise, eat less, eat better
Pharmacotherapy:
Phentermine- stimulates NE release
Dexfenfluramine- incr. secr. of serotonin and decr. reuptake
Sibutramine- block reuptake of NE, ser, dopamine
Rimonabant- Cannabinoid receptor inhibitor
Liraglutide- GLP-1 analog
Orlistat- inhibition of lipase–> no lipid absorp. in intestine

Pharm + behavioral therapy show great efficacy in combo
Bariatric Surgery (last resort): - from restriction methods to malabsorption methods
Lap band (belt on cardiac stomach)
Vertical banded gastroplasty (make stomach a donut, staple at 12 o'clock, band at 9 o'clock)
gastric bypass (skip stomach entirely)
Biliopancreatic diversion with duodenal switch (cut SI in half. connect distal half to stomach. connect proximal half, with gall bladder, back to distal end of distal half before cecum) [most efficacious Sx]