?-Melanocyte-Stimulating Hormone Is a Peripheral, Integrative Regulator of Glucose and Fat Metabolism
Melanocortins are known to affect feeding and probably insulin activity through the central nervous system. It was also recently shown that peripheral ?-melanocyte-stimulating hormone (?-MSH) administration can reduce weight gain in both genetic and diet-induced obese mice. As obesity is often associated with disregulation of glucose and insulin, we investigated the nature of glucose homeostasis in the obese pro-opiomelanocortin (POMC) knockout mouse. Here we report that though they are obese, mice deficient in POMC (and, thereby, deficient in ?-MSH) are euglycemic throughout their lives. While these mice are euinsulinemic, they are hypersensitive to exogenous insulin. This defect can be reversed through administration of ?-MSH. We demonstrate that the actions of ?-MSH in the periphery, known from our work to include lipid metabolism effects, are also involved in glucose homeostasis. These findings substantiate a pivotal role of the POMC gene products in integrating metabolism.
glucose metabolism insulin ?-melanocyte-stimulating hormone (?-msh) obesity pro-opiomelanocortin (pomc) mouse lipid energy homeostasis