Obestity

True or False: obesity is the consequence of small, cumulative imbalances in energy intake and expenditure over longer periods of time

true

What does a calorie restriction do to the body?

increases drive to eat; decreases energy expenditure

True or False: the body favors recovery of lost weight

true

What kind of tool is physical activity in weight loss?

maintenance tool; likely to keep lost weight off

What factors make up metabolic adaptation?

fat mass, fat-free mass, and age

What did we learn from the biggest loser?

all participants experiences a reduction in metabolic rate equivalent to at least one meal per day

weight re-gainers found themselves back to baseline weight and with lessened metabolic rate

it was physical activity and not calories that associated a maintainer vs. re-gainer

What is the source of secretion for ghrelin?

secreted primarily by P/D1 cells in the stomach (fundus)

What is the ghrelin secretion profile over time?

pulsatile and pre-prandial: rises before meals and rapidly suppressed after eating (protein > carb > fat); peaks 30-60 minutes before meals, returns to baselines within 1-2 hours after eating

What is ghrelin’s impact on appetite regulation?

primary hunger hormone, stimulating appetite by activating NPY/AgRP neurons in hypothalamus and increasing food-seeking behavior

What is ghrelin’s impact on diet induced thermogenesis?

reduces DIT by suppressing sympathetic nervous system activity and brown adipose tissue thermogenesis, leading to lower energy expenditure after meals

What is ghrelin’s impact on resting energy expenditure?

decreases REE during fasting or energy restriction, helping the body conserve energy and maintain weight during deficit

What is the source of secretion of GIP?

K-cells in the duodenum and proximal jejunum

What is the secretion profile over time of GIP?

monophasic release; rapid secretion after oral nutrient intake; fat > carb > protein

What is GIP’s impact on appetite regulation?

minimal direct effect on appetite alone, but when co-activated with GLP-1, it may enhance appetite suppression and reduce food intake

What is GIP’s impact on diet induced thermogenesis?

may blunt DIT by promoting energy storage, particularly fat deposition in adipose tissue; may reduce brown fat activity

What is GIP’s impact on resting energy expenditure?

may contribute to energy conservation and lower REE in overnutrition; in combo with GLP-1 agonism it may enhance metabolic efficiency and support weight loss

What is the source of secretion of GLP-1s?

secreted by L-cells in the ileum and proximal colon; released in response to food intake: fat ~ carbs >>> protein

What is the secretion profile over time of GLP-1s?

biphasic release; early peak (neural signs); larger second peak (distal nutrient)

What is GLP-1’s impact on appetite regulation?

strongly suppresses appetite by acting on hypothalamic and brainstem centers, enhances satiety, reduces food intake, and delays gastric emptying

What is GLP-1’s impact on diet induced thermogenesi?

GLP-1 may enhance DIT indirectly by improving insulin sensitivity and modulating gut-brain signals

What is GLP-1s impact on resting energy expenditure?

variable; alone it may have minimal direct impact, but when combined with GIP co-agonism it may support increased energy expenditure and fat oxidation

What is the source of secretion of PYY?

L-cells in the distal small intestine (ileum) and colon; released in response to food intake: fat ~ protein > carbs

What is the secretion profile over time of PYY?

early phase: vagal and endocrine signals before nutrients each the ileum

late phase: directly stimulated by nutrient contact in the distal gut

peaks around 1-2 hours post-meal and remains elevated for several hours

What is PYY’s impact on appetite regulation?

reduces appetite by acting on Y2 receptors in the hypothalamus to inhibit NPY/AgRP neurons and thereby promotes satiety, delaying meal initiation and size

What is PYY’s impact on diet-induced thermogenesis?

may modestly support DIT by slowing gastric emptying and enhancing nutrient sensing in the distal gut, though effects are limited

What is PYY’s impact on resting energy expenditure?

minimal direct effect; may contribute to long-term energy balance by reducing caloric intake and potentially influencing fat oxidation

What is “the U” ?

most weight loss studies have a dip in outcomes around the 8-10 week mark

What is hormonal adaptation to weight loss in the foregut?

hormonal profile is now activated to pro-hunger (ghrelin) and fat storage (GIP)

What is the hormonal adaptation to weight loss in the hindgut?

Hormonal profile is now suppressed for anorexiant signals

What is the net effect of hormonal adaptations to weight loss?

stimulus to onset feeding and less feedback to terminate meal

True or False: gastric bypass and sleeve gastrectomy induce metabolic chnages

true

Which type of bariatric surgery is only a physical restrictive procedure?

gastric band

What happens to ghrelin after bariatric surgery?

it decreases overtime (more with sleeve)

What happens to GLP-1 after bariatric surgery?

it increases (DRASTICALLY with bypass)

What happens to PYY after bariatric surgery?

it increases

What happens to resting metabolic rate with surgery?

no reduction is seen

What part of the brain is the “hub” for feeding onset?

hypothalamus

What neurons stimulate appetite?

AgRP/NPY

What neurons suppress appetite?

POMC/CART

What signals come from adipose tissues?

insulin, leptin

What signals come from the gut?

ghrelin, GIP, GLP-1, PYY

What organizes/signals meal termination?

gastrointestinal vagal afferents

What signals to the brainstem that you are full?

stretch and chemical receptors in the esophagus, stomach, and small intestine

What aspects are a part of the cortex limbic system?

Learn, remember, control, and reward

What are examples of external stimuli and cues?

seeing, smelling, and hearing

What are examples of salience network?

wanting

What is an example of the inhibitory network?

resisting

What is an example of hedonic controls?

pleasure without deficit

What is obesity classified as under the ICD code system?

chronic complex disease

What is the core disease process of obesity?

inflammation

What are the major comorbidities associated with obesity?

T2DM, dyslipidemia, hypertension, coronary heart disease, obstructive sleep apnea, osteoarthritis, cancer, depression and anxiety, gallbladder disease & NAFLD, PCOS, renal failure, GERD, infertility, pregnancy, metabolic syndrome, metabolic syndrome, metabolically healthy obesity

What benefit does weight loss have on metabolic syndrome?

reduces or resolves key features

What benefit does weight loss have on T2DM?

improves glycemic control and can induce remission

What benefit does weight loss have on cardiovascular risk?

reduces blood pressure, LDL, triglycerides; increases HDL

What benefit does weight loss have on sleep apnea?

improves severity of symptoms

What benefit does weight loss have on depression?

mood improvement, particularly with behavioral therapy

What benefit does weight loss have on cancer risk?

believed to reduce the risk of several obesity- related cancers

What is the benefit of 5% weight loss?

clinically meaningful improvements in metabolic health

What is the benefit of 10% weight loss?

multiple organ systems; liver, pancreas, cardiovascular system

What is the benefit of >15% weight loss?

broader and deeper clinical benefits, including disease remission?

What important history should be taken when managing obesity?

weight history, weight gain timeline, past diet attempts, current dietary patterns, diet recall tools, physical activity and functional limitations, weight loss medication history, bariatric surgery history, mental health and eating behaviors, trauma history

What BMI is considered low?

</= 18.5

What BMI is considered normal?

18.5-25.0

What BMI is considered overweight?

25-30

What BMI is considered Class I obesity?

30-35

What BMI is considered Class II obesity?

35-40

What BMI is considered Class III obesity?

>/= 40

What is BMI?

historically the primary tool for measuring obesity; classifying individuals based on weight relative to height

What is waist circumference?

a simple measure of abdominal fat that helps assess central obesity and related health risks

What is waist-to-hip ratio?

a ratio comparing waist and hip measurements to evaluate fat distribution and risk for chronic disease

What is skinfold thickness?

estimates body fat percentage by measuring subcutaneous fat at specific sites using calipers

What is bioelectrical impedance?

estimates body composition by measuring the resistance of body tissues to a small electrical current

What is dual energy X-ray absorptiometry (DEXA)?

imaging method that quantifies bone density, fat mass, and lean body mass

What is pre-clinical obesity?

excess adiposity is present; no current functional impairment in organs, tissues, or quality of life

What is clinical obesity?

excess adiposity is present; there is evidence of dysfunction: organ/tissue damage or impaired physical function; may present as complications or functional limitations

What is anthropometric criteria?

confirmation of excess body fat by at least 1 anthropometric measures other than BMI; pragmatically, reasonable to assume the presence of excess adiposity if BMI >40

What is the management of obesity centered around?

complication-centric approach

What are FDA approved medication options for obesity?

phentermine, orlistat, phentermine/topiramate, lorcaeserin, buproprion/naltrexone, semaglutide, tirzepatide

What is the MOA of phentermine (Adipex)?

increases release and inhibits reuptake of norepinephrine (lesser extent dopamine) and thereby stimulates POMC neurons to suppress appetite

What is the MOA of orlistat (Xenical)

binds gastric and pancreatic lipases in lumen of the stomach and small intestine and thereby reduces fat absorption into the body

What is the MOA of phentermine/topiramate (Qsymia)?

topiramate: inhibits NPY/AgRP synaptic releases of GABA that plays a role in inhibiting POMC neurons; inhibiting the release of GABA reduces the suppression of POMC neurons and thereby increases appetite suppression

What is the MOA of bupropion/naltrexone (Contrave)?

bupropion: increases the release and inhibits the reuptake of dopamine and to lesser extent norepinephrine thereby stimulating OPMC neurons to suppress appetite

naltrexone: opiate receptor blockade prevents b-endorphin binding that tonically inhibits POMC neurons; reduction of dopamine in reward centers influences desires, palatability

What is the MOA of GLP-1s?

stimulates POMC neurons to suppress appetite; decreases gastric emptying thereby stimulating vagal afferents for meal termination

What GLP-1s are approved for weight loss?

liraglutide (saxenda)

semaglutide (ozempic/wegovy)

tirzepatide (Zepbound)

What did the STAMPEDE study show?

gastric bypass (more so) and sleeve gastrectomy lead to use of way less diabetes drugs post-surgery