Leptin Signaling
Adipocyte hormone signaling to the hypothalamus regulating energy balance.
Overview
Leptin is an adipokine secreted in proportion to fat mass. It signals through the long-form leptin receptor (LepRb) in the hypothalamus, primarily in the arcuate nucleus. LepRb activates JAK2-STAT3, PI3K-AKT, and SHP2-ERK pathways. Leptin activates anorexigenic POMC/CART neurons (reducing appetite) and inhibits orexigenic AgRP/NPY neurons (which increase appetite). SOCS3 and PTP1B are negative regulators whose upregulation contributes to leptin resistance in obesity.
Cellular Location
Adipose tissue → Hypothalamus (arcuate nucleus)
Clinical Significance
Leptin deficiency causes severe obesity (treated with metreleptin); most obese individuals have leptin resistance; MC4R mutations are the most common monogenic obesity cause; leptin connects energy stores to reproduction.
Key Molecules
Key Enzymes
Related Pathways
JAK-STAT Pathway
Cytokine-driven signaling from receptor to gene expression via STAT dimerization.
PI3K/AKT/mTOR Pathway
Regulates cell survival, growth, and metabolism via phosphoinositide signaling.
AMPK Pathway
Cellular energy sensor activating catabolic and inhibiting anabolic pathways.
Insulin Signaling Pathway
Insulin receptor activation driving glucose uptake and anabolic metabolism.