Leptin

Leptin is a peptide hormone produced primarily by adipocytes, especially in white adipose tissue. Its circulating concentration generally reflects the amount of stored body fat, although it also changes with short-term energy availability. Leptin acts as a signal from adipose tissue to the brain and other organs, helping coordinate energy balance with the body's stored energy reserves .^1,2

In the brain, leptin acts on receptors in the hypothalamus and related neural circuits involved in food intake, energy expenditure, and neuroendocrine function. When energy stores or energy intake fall, circulating leptin concentrations decrease. This decline contributes to physiological adaptations to energy shortage, including increased hunger and reduced energy expenditure. Leptin therefore functions importantly as a signal of insufficient energy availability rather than simply as a hormone that produces fullness after a meal .^1,2

Leptin signals through the leptin receptor, with the long receptor isoform, often called LepRb, responsible for many of its major physiological effects. This receptor activates intracellular signaling pathways including the JAK-STAT pathway. Leptin-responsive neural circuits interact with several other systems that regulate feeding and metabolism, so leptin is one component of a larger energy-homeostasis network rather than a single controller of body weight .^1,2

Leptin deficiency and leptin resistance are distinct. Rare genetic defects that prevent normal leptin production can cause profound hyperphagia and severe early-onset obesity. In common obesity, however, circulating leptin is usually elevated rather than deficient because fat mass is increased. A reduced biological response despite elevated leptin concentrations is commonly described as leptin resistance .^1,2