Lecture 22: Energy balance and Obesity

Leptin

Adipocytes proportional to fat stores

Ghrelin

Cyclic pro hunger signal stomach to CNS, drops with feeding

Adiponectin

Mainly produced in adipocytes

Increases insulin sensitivity

Increases fatty acid oxidation in liver and skeletal muscle

Decreases vascular inflammation

Hypothalamic circuits

POMC/CART anorexigenic neurons

NPY/AgRP orexigenic neurons

Catabolic Efferent Signals – Burn Energy

BDNF – behavioral modification

CRH – HPA axis

TRH - promote thyroid hormone release

Anabolic Efferent Signals – Seek food

MCH - behavioral modification

GIP, GLP-1

Incretins

Hormone proteins produced in intestine in response to feeding

GIP produced in K cells in small intestine in response to nutrients

GLP1 produced in L cells in small intestine in response to nutrients

Catabolic

Reduce blood glucose

Increase insulin sensitivity

Reduce appetite

Slow gastric emptying

Decrease bone resorption and formation

Increase fat storage

Dual receptor agonist

Effects of obesity on energy balance

Obesity creates a positive feedback loop in the energy balance circuit

Body becomes resistant to leptin

Insulin – resistance and hyperinsulinemia

Ghrelin – Decreased levels → Levels increase with weight loss making dieting difficult

Adiponectin – Decreased

Obstructive sleep apnea

mechanical obstruction of airway during sleep

Neck fat causes airway collapse when muscle tone relaxes during sleep

Apnea → CO2 ↑ → arousal, increased muscle tone, breathing

May also be caused by tonsillar hypertrophy

Daytime sleepiness, morning headache

Loud snoring, gasping, choking, snorting, or interruptions in breathing while sleeping

Diagnosis – polysomnography

Complications include pulmonary hypertension, atrial fibrillation, accidents

Treated with continuous positive airway pressure (CPAP)

Obesity hypoventilation syndrome

alveolar hypoventilation

Obesity restricts movement of diaphragm and chest wall

Hypoventilation during the day and night

Fatigue, dyspnea, depression

↑ CO2 while awake

Often associated with OSA

Obesity increases the risk of many cancers

Endometrial, Esophageal adenocarcinoma, Gastric cardia, liver, kidney, meningioma, pancreatic, colorectal, gallbladder, breast, ovarian, thyroid

Mechanisms:

Steroid hormones – estradiol (estrogen) converted in adiposities

Inflammation via glycosylation, oxidative stress and FFA effects

2’ effects (GERD, NAFL)

Direct insulin effects

Hyperinsulinemia and cancer

Insulin inhibits sex hormone binding globulin (SHBG) increasing bioavailability of estrogen

Insulin-IR signaling PI3K/AKT/mTOR promotes cell growth and proliferation

IGF-R1 triggers multiple cell proliferation pathways

Hybrid receptor (IGF-1R/IR) triggered by insulin, activates IGF-R1 transmembrane domains