Central melanocortin receptors regulate insulin action

Energy balance and insulin action are tightly coregulated. Leptin regulates energy intake and expenditure partly by modulation of the melanocortin pat hway in the hypothalamus. Here we demonstrate potent effects of the melanoc ortin pathway on insulin action and body distribution of adiposity. Conscio us rats received week-long infusions of either a melanocortin receptor agon ist, alpha -melanocyte-stimulating hormone (alpha -MSH), or antagonist, SHU 9119, in the third cerebral ventricle while food intake was maintained cons tant in each group. alpha -MSH decreased intra-abdominal fat and markedly e nhanced the actions of insulin on both glucose uptake and production, while SHU9119 exerted opposite effects. Our findings elucidate a neuroendocrine network that is likely to play a central role in the coupling of energy int ake and insulin action.