The Leptin Receptor, scientifically known as OB-R or LEPR, is a transmembrane protein primarily found in the hypothalamus of the brain, as well as on various peripheral cells, that binds to the adipokine hormone leptin. Leptin, secreted by adipose tissue, signals the body’s energy stores to the central nervous system, and the receptor’s function is to transmit this crucial signal of satiety and long-term energy homeostasis. The long isoform, OB-Rb, possesses the complete intracellular signaling domain necessary to elicit a biological response. Defects in this receptor or chronic resistance to its signaling can lead to severe metabolic dysregulation and obesity.
Origin
The receptor was discovered shortly after its ligand, leptin (from the Greek leptos, meaning “thin”), was identified in 1994. The receptor’s designation, OB-R, is derived from the obese gene, which encodes the leptin protein itself. Its study originates in the field of neuroendocrinology, focusing on the afferent signals that regulate body weight and energy balance. The identification of its specific signaling pathway provided a molecular target for understanding metabolic disorders.
Mechanism
The mechanism of action is a classic cytokine-receptor signaling cascade, predominantly involving the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway. Upon leptin binding, the OB-Rb receptor dimerizes and activates the associated Janus kinase 2 (JAK2). Activated JAK2 then phosphorylates tyrosine residues on the receptor’s intracellular tail, creating docking sites for STAT proteins, most notably STAT3. Phosphorylated STAT3 then dimerizes, translocates to the nucleus, and modulates the transcription of genes that control appetite, energy expenditure, and neuroendocrine function, such as the production of anorexigenic neuropeptides.
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