Leptine

Leptine, or leptin in English, is a hormone produced predominantly by white adipose tissue. In humans the LEP gene encodes leptin, while the ob gene was identified in mice. Circulating leptin levels rise with increasing fat mass and fall with weight loss, making it a central signal of energy stores to the brain.

Leptin acts mainly in the hypothalamus by binding to leptin receptors (LepR), especially the long form LepRb. This activates intracellular pathways such as JAK2-STAT3 and, to a lesser extent, PI3K and MAPK. In the arcuate nucleus, leptin stimulates anorexigenic POMC/CART neurons and inhibits orexigenic NPY/AgRP neurons, reducing appetite and promoting energy expenditure. Leptin also influences reproductive function, bone metabolism, and immune responses.

Regulation: leptin production reflects adiposity and is modulated by insulin, glucocorticoids, and inflammatory signals. Leptin must cross the blood–brain barrier via a transport system to reach central targets. In obesity, despite high leptin levels, signaling is blunted—a condition termed leptin resistance, contributing to continued weight gain.

Clinical aspects: congenital leptin deficiency caused by LEP mutations leads to severe early-onset obesity and endocrine problems; metreleptin, a recombinant leptin, is approved for this condition and for generalized lipodystrophy. In typical obesity, leptin therapy is not effective due to resistance, although research investigates strategies to restore leptin sensitivity.

Discovery: leptin was identified in 1994 by Friedman and colleagues, transforming understanding of energy homeostasis.