The hypothalamic melanocortin system plays a central role in energy homeostasis. Which of the following correctly describes how leptin and NPY/AgRP neurons interact within the arcuate nucleus to regulate food intake?

• A Leptin inhibits POMC/CART neurons and activates NPY/AgRP neurons, creating a net orexigenic signal to compensate for adiposity
• B Leptin activates POMC/CART neurons (anorexigenic) and inhibits NPY/AgRP neurons (orexigenic); both effects reduce food intake and increase energy expenditure ✓
• C Leptin acts exclusively on NPY/AgRP neurons via LepRb receptors, reducing NPY secretion while POMC neurons are regulated only by ghrelin
• D Leptin activates POMC neurons but has no direct effect on NPY/AgRP neurons, which are regulated solely by insulin

Explanation

Leptin, secreted proportionally to adipose mass, acts on LepRb receptors in arcuate nucleus neurons: it activates anorexigenic POMC/CART neurons (releasing alpha-MSH, which acts on MC4R to reduce appetite) and simultaneously inhibits orexigenic NPY/AgRP neurons. AgRP antagonises MC4R, so its suppression further amplifies the anorexigenic signal. Net effect: reduced food intake and increased sympathetic-mediated energy expenditure. In leptin deficiency (e.g., congenital leptin deficiency), both effects are lost, producing severe hyperphagia and obesity.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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