THE BIOLOGY OF LEPTIN - A REVIEW

Leptin, a 16-kDa protein secreted from white adipocytes, has been impl icated in the regulation of food intake, energy expenditure, and whole -body energy balance in rodents and humans. The gene encoding leptin w as identified by positional cloning and is the mutation leading to the profound obese phenotype of the ob/ob mouse. Exogenous administration of leptin to ob/ob mice leads to a significant improvement in reprodu ctive and endocrine status as well as reduced food intake and weight l oss. The expression and secretion of leptin is highly correlated with body fat mass and adipocyte size. Cortisol and insulin are potent stim ulators of leptin expression, and expression is attenuated by beta-adr energic agonists, cAMP, and thiazolidinediones. The role of other horm ones and growth factors in the regulation of leptin expression and sec retion is emerging. Leptin circulates specifically bound to proteins i n serum, which may regulate its half-life and biological activity. Iso forms of the leptin receptor, members of the interleukin-6 cytokine fa mily of receptors, are found in multiple tissues, including the brain. Many of leptin's effects on food intake and energy expenditure are th ought to be mediated centrally via neurotransmitters such as neuropept ide Y. Multiple peripheral effects of leptin have also been recently d escribed, including the regulation of insulin secretion by pancreatic beta cells and regulation of insulin action and energy metabolism in a dipocytes and skeletal muscle. Leptin is thought to be a metabolic sig nal that regulates nutritional status effects on reproductive function . Leptin also plays a major role in hematopoeisis and in the anorexia accompanying an acute cytokine challenge. The profound effects of lept in on regulating body energy balance make it a prime candidate for dru g therapies for humans and animals.