Leptin, secreted by white adipose tissue in proportion to fat mass, reduces food intake through which primary central mechanism?

• A Inhibits orexigenic NPY/AgRP neurons and activates anorexigenic POMC/CART neurons in the arcuate nucleus of the hypothalamus ✓
• B Directly suppresses insulin secretion from pancreatic beta cells, reducing anabolic drive
• C Stimulates cholecystokinin (CCK) release from duodenal I-cells to signal satiety
• D Activates the ventromedial hypothalamus via GLP-1 receptor pathway

Explanation

Leptin acts on the arcuate nucleus via LepRb (long-form receptor). It inhibits NPY (neuropeptide Y) and AgRP (agouti-related peptide) neurons — which normally stimulate appetite and reduce energy expenditure — and simultaneously activates alpha-MSH-producing POMC (pro-opiomelanocortin) and CART neurons that suppress appetite via MC4R signalling. Ob/ob mice lacking leptin are obese, and peripheral leptin injection restores normal body weight. CCK is a short-term satiety signal from gut, not primarily a leptin effector.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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