What BMI increases the risk of death from CV disease and cancer in men and women?
Underweight (less than 18.5)
and overweight (25-29.9), obese (30-34.9), obesity II (35-39.9) and extreme obesity (40+)
What waist circumference places one at an increased risk of CV related disease?
Men: 40+ in
Women: 35+ in
Does obesity have a genetic component?
Yes, twin studies show 50% concordance of obesity
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?
Leptin or leptin receptor deficiency
POMC gene mutations
Prohormone convertase-1 mutations
Thyroid hormone receptor-B mutations
What are some substances that promote weight gain?
Other things that promote weight gain?
Orexin A and B
What are some substances that promote weight loss?
Other weight loss promoting drugs?
Leptin (made in fat)
Insulin (inhibits appetite)
Corticotropin-releasing hormone (CRH)
Cocaine-amphetamine-regulated peptide (CART)
Ciliary neurotrophic factor
What is the endocannabinoid system?
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
How does Pentermine work for obesity treatment?
It stimulates nor release
How does Dexfenfluramine work for obesity treatment?
It increases the release of serotonin
How does Fenfluramine work for obesity treatment?
It decreases uptake of serotonin uptake
How does Lorcaserin work for obesity treatment?
It is a 5HT2c receptor agonist
How does Sibutramine work for obesity treatment?
It blocks nor, serotonin, and dopamine reuptake
How does Rimonabant work for obesity treatment?
It is a cannabinoid receptor inhibitor
How does Liraglutide work for obesity treatment?
It is a GLP-1 analog
What does orlistat do?
Inhibits lipase action in the GI to treat obesity
Does modest weight loss (5-10%) help at all in obese pts with HTN, type II diabetes, or dyslipidemia?
Yes, it results in:
–Improved diabetes control (remission ~16%)
–Improved blood pressure control
–Improved lipid profile
–Need for fewer medications
How does leptin work?
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
Note about fecal transplants
There is accumulating evidence that fecal transplants from thin mice into obese mice can reverse signs of obesity
What are some co-morbidities associated with obesity?
HTN, CVD, stroke
Describe the pathopshyi of obesity leading to heart failure?
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
How does increased sympathetic tone lead to HTN?
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
How would obesity lead to gallstones?
obesity increased estrogen which increased cholesterol turnover/excretion leading to risk of gallstones (and cancer)
Which bariatric surgery results in the greatest initial wgt. loss?
Biliopancreatic diversion (39%)
Roux-en-y gastric bypass (34.9%)
Mortality Benefit of Bariatric Surgery?
•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.
AEs of bariatric surgery?
micronutrient deficits, hypoglycemia, and waning effects