leptina

Leptin is a peptide hormone produced predominantly by adipocytes in white adipose tissue. It functions as a hormonal signal of energy stores, circulating in proportion to body fat and acting mainly on receptors in the hypothalamus to regulate appetite and energy expenditure. The leptin gene (LEP) encodes the protein, which is secreted into the bloodstream and crosses the blood–brain barrier to reach its target neurons.

Leptin acts primarily through the leptin receptor (LEPR), particularly the long form LEPRb, expressed in several brain regions including the arcuate nucleus of the hypothalamus. Binding of leptin activates signaling pathways such as JAK-STAT, PI3K, and MAPK, influencing neuronal activity. In the hypothalamus, leptin promotes anorexigenic (appetite-suppressing) pathways by stimulating POMC/CART neurons and inhibiting NPY/AGRP neurons, thereby reducing food intake and increasing energy expenditure. This system forms a feedback loop that links adipose tissue mass to feeding behavior and metabolism.

Physiological roles extend beyond energy balance to reproduction, immune function, and bone metabolism. Leptin deficiency, due to rare genetic mutations, causes severe hyperphagia and early-onset obesity, as well as immune and developmental issues. In contrast, most common obesity is associated with elevated leptin levels and leptin resistance, where signaling is impaired despite high circulating concentrations.

Therapeutically, recombinant leptin (metreleptin) is approved for certain conditions, including congenital leptin deficiency and generalized lipodystrophy. In general obesity, leptin therapy has limited efficacy due to resistance, and research continues into mechanisms to restore leptin sensitivity.