leptinbinding

Leptin binding refers to the process by which the hormone leptin interacts with its receptor and related binding proteins to regulate energy balance and metabolism. Leptin is produced by adipose tissue in proportion to fat mass and acts as a hormonal signal of energy stores to the brain.

The biologically active interaction occurs mainly when leptin binds to leptin receptors, particularly the long form LepRb, expressed in hypothalamic neurons and other tissues. Binding activates intracellular signaling via JAK2-STAT3, with additional engagement of PI3K-AKT and MAPK pathways. This signaling alters the transcription of neuropeptides that control appetite and energy expenditure, increasing anorexigenic signals like POMC and CART while reducing orexigenic signals such as NPY and AgRP. The overall effect is reduced food intake and increased energy expenditure.

Circulating leptin binding is modulated by soluble receptor forms and other binding proteins. A soluble leptin receptor can bind leptin in the bloodstream, influencing leptin’s bioavailability and half-life. The balance between free and bound leptin contributes to the hormonal signal received by the brain and peripheral tissues.

Physiologically, leptin binding coordinates short-term feeding behavior with long-term energy stores. It also impacts sympathetic tone, reproductive function, and immune responses. In obesity, elevated leptin levels often coincide with leptin resistance, reducing sensitivity to binding and signaling despite high circulating hormone. Conversely, congenital leptin deficiency or LEPR mutations disrupt binding and signaling, leading to severe early-onset obesity but can be responsive to leptin replacement or targeted therapies.

Research on leptin binding employs binding assays and receptor studies to characterize affinity, specificity, and downstream signaling, advancing understanding of metabolic regulation and potential interventions.