LEPTIN AND OTHER SECRETORY PRODUCTS OF ADIPOCYTES MODULATE MULTIPLE PHYSIOLOGICAL FUNCTIONS

The view that the adipocyte acts only as a passive storage site for en ergy in the form of triglyceride has been rendered obsolete by the dis covery that adipocytes secrete a variety of metabolically active molec ules. These molecules include free fatty acids, which decrease the rat e of glucose oxidation by peripheral tissues; adipsin and other comple ment factors involved in host defense; tumor necrosis factor alpha, wh ich may be an important determinant of insulin sensitivity; and angiot ensinogen, which appears to promote terminal differentiation of preadi pose to adipose cells. Leptin, a 167 amino acid polypeptide encoded by the obese gene, is a recently described adipocyte secretory product t hat communicates the status of the body's energy reserve to the centra l nervous system, apparently for the purpose of regulating body compos ition. Plasma leptin levels are exponentially related to total adipose mass. Daily injection of leptin into ob/ob mice leads to decreased fo od consumption and increased energy expenditure, both of which result in loss of adipose mass. Leptin-treated animals also have lower circul ating insulin and glucose levels than pair fed controls. Finally, lept in corrects the infertility of ob/ob mice by restoring gonadotropin se cretion to normal. These observations indicate that the adipocyte play s a key role in energy balance, insulin action, host defense, and repr oduction, and suggest new approaches for understanding several importa nt human diseases.