Leptin

Class

Recombinant leptin analog

Leptin is a hormone secreted by fat (adipose) tissue in proportion to fat mass, functioning as the body's principal signal of long-term energy reserves. It acts primarily on neurons in the hypothalamus, a brain region that governs appetite and energy balance, by binding the leptin receptor. When leptin is absent or nonfunctional, as occurs in certain rare genetic and acquired forms of lipodystrophy (a condition marked by loss of adipose tissue), the brain perceives a state of starvation regardless of actual body fat, driving severe hunger and disrupting glucose and lipid metabolism. Replacing leptin, or activating its receptor directly, restores this signaling and can correct both the behavioral (appetite) and metabolic (blood sugar, triglyceride) abnormalities that result from its absence. This mechanism is distinct from common obesity, where leptin is typically abundant but the brain becomes less responsive to it, a phenomenon known as leptin resistance. The therapeutic rationale therefore centers on conditions of genuine leptin deficiency or receptor underactivation rather than on obesity broadly. Approaches include a recombinant protein version of the hormone itself and, separately, small molecules designed to engage the leptin receptor pathway without requiring injection of the native protein.