LEPTIN SELECTIVELY DECREASES VISCERAL ADIPOSITY AND ENHANCES INSULIN ACTION

Intraabdominal adiposity and insulin resistance are risk factors for d iabetes mellitus, dyslipidemia, arteriosclerosis, and mortality, Lepti n, a fat-derived protein encoded by the ob gene, has been postulated t o be a sensor of energy storage in adipose tissue capable of mediating a feedback signal to sites involved in the regulation of energy homeo stasis, Here, we provide evidence for specific effects of leptin on fa t distribution and in vivo insulin action, Leptin (LEP) or vehicle (CO N) was administered by osmotic minipumps for 8 d to pair-fed adult rat s. During the 8 d of the study, body weight and total fat mass decreas ed similarly in LEP and in CON, However, while moderate calorie restri ction (CON) resulted in similar decreases in whole body (by 20%) and v isceral (by 21%) fat, leptin administration led to a specific and mark ed decrease (by 62%) in visceral adiposity. During physiologic hyperin sulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of gluco se uptake, Finally, leptin exerted complex effects on the hepatic gene expression of key metabolic enzymes and on the intrahepatic partition ing of metabolic fluxes, which are likely to represent a defense again st excessive storage of energy in adipose depots, These studies demons trate novel actions of circulating leptin in the regulation of fat dis tribution, insulin action, and hepatic gene expression and suggest tha t it may play a role in the pathophysiology of abdominal obesity and i nsulin resistance.