Leptin cellular actions are mediated by leptin receptors (OB-Rs, Leptin R), which are membrane-anchored molecules binding to leptin and transducing its intracellular signal. Leptin R is encoded by the db gene. Leptin R is a member of cytokine receptor family that including various interleukins, interferon-γ, erythropoietin, growth hormone and prolactin. Proteolytic cleavage of transmembrane Leptin R produces a soluble leptin binding protein called soluble leptin receptor (sOB-R), which constitutes the major binding protein of circulating leptin in human plasma. The sOB-R exerts high affinity in binding leptin, antagonizing the membrane leptin receptors and, functionally, inactivating leptin. By binding circulating leptin, sOB-R modulates the bioavailability and efficacy of leptin, exerting a predominantly inhibitory effect on leptin signal transduction; thus, altering the sensitivity of target tissues to leptin actions and producing a state called leptin resistance in analogy to in sulin resistance. Genetic deficiency of either leptin or Leptin R causes severe obesity and obesity-associated diabetes.
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