leptin

Leptin is produced by white adipose tissue and circulates in proportion to fat mass, signaling energy sufficiency to the brain. It binds leptin receptors (Ob-R) in the arcuate nucleus of the hypothalamus, activating anorexigenic neurons (POMC/CART) and inhibiting orexigenic neurons (NPY/AgRP), thereby decreasing appetite and increasing energy expenditure via sympathetic activation. Leptin also influences neuroendocrine function, including permissive effects on the hypothalamic-pituitary-gonadal axis; leptin deficiency (as in congenital leptin deficiency or hypothalamic amenorrhea from low body fat, e.g., in anorexia nervosa or female athletes) causes hypogonadotropic hypogonadism. In starvation, leptin levels fall, signaling energy deficit and triggering adaptive responses (increased appetite, decreased thyroid hormone/reproductive function to conserve energy). In obesity, leptin levels are elevated, but most individuals develop leptin resistance—an impaired hypothalamic response despite high circulating leptin, analogous to insulin resistance in type 2 diabetes. Rare mutations in the leptin gene (ob gene) or leptin receptor cause severe early-onset obesity due to unopposed hyperphagia; recombinant leptin therapy is effective only in these rare congenital leptin-deficient patients, not in common obesity. Leptin is regulated by insulin (increases leptin) and fasting (decreases leptin), and it has additional roles in immune function, bone metabolism, and angiogenesis. Key boards testing points: distinguishing leptin (adipose-derived, satiety signal) from ghrelin (stomach-derived, hunger signal); understanding leptin resistance in obesity; and recognizing hypothalamic amenorrhea due to low leptin in low body fat states.