Endocrine Weight Loss Cortisol, Stress Hormones, and Body Composition 1 — Questions and Answers
Question 1: Chronic elevation of cortisol promotes central (visceral) obesity primarily through which mechanism?
- Stimulating adiponectin release from visceral fat
- Activating glucocorticoid receptors in visceral adipocytes, promoting fat uptake and inhibiting lipolysis (Correct answer)
- Increasing leptin synthesis in subcutaneous adipose tissue
- Suppressing insulin secretion from pancreatic beta cells
Correct answer: Activating glucocorticoid receptors in visceral adipocytes, promoting fat uptake and inhibiting lipolysis
Visceral adipocytes express high levels of glucocorticoid receptors and 11β-HSD1 (which converts cortisone to cortisol locally), making them especially sensitive to cortisol's fat-accumulating effects.
Question 2: Cushing's syndrome due to a pituitary ACTH-secreting adenoma is called Cushing's disease and produces the classic body composition change of:
- Generalized fat loss with muscle hypertrophy
- Central obesity with proximal muscle wasting, moon face, and buffalo hump (Correct answer)
- Peripheral obesity with distal muscle weakness
- Symmetrical subcutaneous fat gain without muscle loss
Correct answer: Central obesity with proximal muscle wasting, moon face, and buffalo hump
Chronic glucocorticoid excess in Cushing's syndrome causes redistribution of fat to central, facial, and dorsocervical depots while simultaneously causing protein catabolism and proximal muscle wasting.
Question 3: The 1 mg overnight dexamethasone suppression test is used to screen for Cushing's syndrome. An abnormal result is a morning cortisol of:
- <1.8 mcg/dL (suppressed normally)
- >1.8 mcg/dL (failure to suppress) (Correct answer)
- >5 mcg/dL only
- <5 mcg/dL
Correct answer: >1.8 mcg/dL (failure to suppress)
A morning serum cortisol >1.8 mcg/dL after 1 mg dexamethasone the night before indicates failure of hypothalamic-pituitary-adrenal axis suppression, warranting further workup for Cushing's syndrome.
Question 4: Psychological stress promotes weight gain through cortisol's effect on:
- Directly inhibiting adipocyte lipolysis and increasing cravings for high-calorie foods (Correct answer)
- Stimulating thermogenesis in brown adipose tissue
- Reducing NPY in the hypothalamus and suppressing appetite
- Increasing adiponectin and improving insulin sensitivity
Correct answer: Directly inhibiting adipocyte lipolysis and increasing cravings for high-calorie foods
Stress-induced cortisol elevates appetite (particularly for calorie-dense, rewarding foods), inhibits lipolysis, and promotes visceral fat deposition through glucocorticoid receptor activation.
Question 5: Which enzyme locally amplifies cortisol concentration within adipose tissue, particularly visceral fat?
- Aromatase (CYP19A1)
- 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) (Correct answer)
- 17β-hydroxysteroid dehydrogenase
- Cortisol-binding globulin (CBG)
Correct answer: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
11β-HSD1 regenerates active cortisol from inactive cortisone within fat tissue; its overexpression in visceral adipose tissue amplifies glucocorticoid action locally and contributes to central obesity.
Question 6: Epinephrine (adrenaline) released during acute stress primarily affects body composition acutely by:
- Stimulating fat cell differentiation and lipogenesis
- Activating beta-adrenergic receptors on adipocytes to stimulate lipolysis and mobilize free fatty acids (Correct answer)
- Inhibiting glucagon and promoting glycogen storage
- Increasing leptin secretion from adipocytes
Correct answer: Activating beta-adrenergic receptors on adipocytes to stimulate lipolysis and mobilize free fatty acids
Epinephrine activates beta-adrenergic receptors on adipocytes, stimulating hormone-sensitive lipase and triglyceride lipase, releasing free fatty acids and glycerol into circulation for rapid fuel use.
Endocrine Weight Loss Cortisol, Stress Hormones, and Body Composition 1
Chronic elevation of cortisol promotes central (visceral) obesity primarily through which mechanism?