IS LEPTIN THE LINK BETWEEN OBESITY AND INSULIN-RESISTANCE

Leptin is the product of OB gene. This 16 kDa protein is produced by m ature adipocytes and is secreted in plasma. its plama levels are stron gly correlated with adipose mass in rodents as well as in humans. Lept in inhibits food intake, reduces body weight and stimulates energy exp enditure. It has been suggested that leptin could be the link between obesity and diabetes. Recent, experiments in rodents have shown that l eptin expression in adipocytes is also regulated at short-term by horm ones and nutrients. Leptin expression increases after food intake and decreases during fasting and diabetes. Insulin and glucocorticoids inc rease leptin expression, whereas catecholamines, via beta-adrenergic r eceptors and cAMP, and long-chain fatty acids (and thiazolidinediones) , via PPARy, inhibit leptin expression. Leptin is a cytokine that hind s to transmembrane receptors similar to the receptors of cytokine fami ly (type IL-6), and transmit their information inside the cell, after dimerisation. A short-form of leptin receptor (with a cytoplasmic doma in of 34 amino residues) has been identified in the choroid plexus. Th is type bf receptor should be used for leptin transport across the blo od-brain barrier. Then leptin binds to a long-form of leptin receptor in the hypothalamus (with a cytoplasmic domain of 302 amino residues) and decreases the production of neuropeptide Y, a neuromediator of foo d intake. The long-form of leptin receptor, transmits its information via the Janus Kinases (JAK) who subsequently phosphorylate transcripti on factors of the STAT family. Intermediary forms of leptin receptor h ave been identified in other tissues: fiver, heart, skeletal muscles, endocrine pancreas. The role of leptin receptors in these tissues rema ins obscure, but is of considerable interest. Recent studies have show n that leptin inhibits insulin secretion and have anti-insulin effects on liver and adipose tissue. If these effects are confirmed, leptin c ould play a role similar to TNF alpha and could participate in the ins ulin-resistance of obesity and type II diabetes.