Introduction: Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide which is located in the lateral hypothalamus and regulate the energy balance. MCH deficient mice are hypophagic, lean and do not develop hepatosteatosis when fed on high fat diet. The MCH increases food intake and adiposity, so we sought to investigate the role of the MCH on adipocyte and hepatic metabolism.
Methods: MCH were chronically administered into the lateral ventricles of rats brain, using osmotic pumps that released the MCH for a week. To study whether the sympathetic nervous system mediates the actions of MCH on white adipose tissue, deficient mice for the three beta-adrenergic receptors were used (triple knockout mice). To determine whether the central effect of MCH on the liver was mediated through the parasympathetic nervous system (PSNS), the vagus nerve was dissected. Adenoviral particles overexpressing MCH receptors (MCH-R) were estereotaxically administered into arcuate and lateral hypothalmus (LHA, ARC). Tissues were analyzed to determine the expression of genes and proteins involved in lipid metabolism of liver and fat.
Results: The activation of MCH receptors (MCH-R) promotes the liver fat storage through the parasympathetic nervous system (PSNS), whereas it increases lipid deposition in WAT via the suppression of sympathetic traffic. These metabolic actions are independent of parallel changes in food intake and energy expenditure. Genetic activation of MCH-R increases body weight gain and food intake, specifically in the LHA modulated hepatic lipid metabolism, whereas the specific activation of this receptor in the arcuate nucleus affected adipocyte metabolism.
Conclusions: Central MCH system increases lipid storage via modulation of adipocyte and hepatic metabolism. Activation of MCH-R in the ARC control adipocyte lipid metabolism via a SNS-dependent mechanism, while the activation of MCH-R in the LHA influences hepatic lipid metabolism through the PSNS.
27 Apr - 01 May 2013
European Society of Endocrinology