|Houseknecht, Karen - PURDUE UNIVERSITY|
|Baile, Clifton - UNIVERSITY OF GEORGIA|
|Spurlock, Michael - PURINA MILLS, INC.|
Submitted to: Journal of Animal Science
Publication Type: Review Article
Publication Acceptance Date: January 8, 1998
Publication Date: N/A
Technical Abstract: Leptin, a 16 kDa protein secreted from white adipocytes, has been implicated in regulation of food intake, energy expenditure and whole-body energy balance in rodents and humans. A mutation in the gene encoding leptin leads to the profound obese phenotype of the ob/ob mouse. Exogenous administration of leptin to ob/ob mice leads to significant improvement in reproductive and endocrine status as well as reduced food intake and weigh loss. Expression and secretion of leptin is highly correlated with body fat mass and adipocyte size. Cortisol and insulin are potent stimulators of leptin expression while expression is attenuated by beta-adrenergic agonists, cAMP and thiazolidinediones. The role of other hormones and growth factors in the regulation of leptin expression and secretion is emerging. Leptin circulates specifically bound to proteins in serum which may regulate its half-life and biological activity. Isoforms of the leptin nreceptor, members of the IL-6 cytokine family of receptors, are found in multiple tissues including the brain. Many of leptin's effects on food intake and energy expenditure are thought to be mediated centrally via neurotransmitters such as neuropeptide Y. Multiple peripheral effects of leptin have also been recently described including the regulation of insulin secretion by pancreatic beta cells and insulin action in adipocytes and skeletal muscle. Leptin is thought to be a metabolic signal which 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 leptin on regulating body energy balance make it a prime candidate for drug therapies for humans and animals.