leptins

Leptin is a peptide hormone produced predominantly by white adipose tissue that helps regulate energy balance by inhibiting hunger and modulating energy expenditure. Circulating leptin levels reflect body fat content, rising with greater fat mass and falling with fasting. It is secreted by adipocytes and travels to the brain, where it binds to leptin receptors in the hypothalamus and other tissues.

In the brain, leptin activates signaling pathways through the long-form leptin receptor (LEPRb), chiefly in hypothalamic neurons. This signaling suppresses orexigenic neurons that produce neuropeptide Y (NPY) and agouti-related peptide (AgRP) and stimulates anorexigenic neurons that produce pro-opiomelanocortin (POMC). The net effect is reduced appetite and increased energy expenditure, mediated in part by the JAK-STAT pathway and related signaling cascades. Leptin also acts on receptors outside the brain, influencing reproductive function, bone metabolism, and immune and metabolic processes.

Physiologically, leptin serves as a signal of energy sufficiency to help maintain body weight. In obesity, high leptin levels are common, but a state of leptin resistance often blunts its regulatory effects, contributing to continued weight gain. Leptin therapy is effective for congenital leptin deficiency and for generalized lipodystrophy; metreleptin is approved for certain such indications. By contrast, leptin monotherapy is not generally effective for common obesity due to resistance and the multifactorial nature of energy balance.

Leptin levels are also used as a biomarker of adiposity and nutritional status in research and clinical settings. The hormone was discovered in 1994 by Jeffrey Friedman and colleagues, significantly advancing understanding of energy homeostasis and metabolic regulation.