Endocrine Abstracts (2013) 32 P681 | DOI: 10.1530/endoabs.32.P681

Hypothalamic melanin-concentrating hormone influences liver and adipose lipid metabolism

Monica Imbernon1,2, Daniel Beiroa1,2, Maria J Vazquez1,2, Donald A Morgan3, Christelle Veyrat-Durebex4, Begoña Porteiro1,2, Adenis Diaz-Arteaga1,2, Ana Senra1,2, Omar Al-Massadi1,2, Douglas A Velasquez1, Rosalia Gallego5, Luisa M Seoane6, Miguel Lopez1, Roger J Davis7, Guadalupe Sabio8, Françoise Rohner-Jeanrenaud4, Kamal Rahmouni3, Carlos Dieguez1,2 & Ruben Nogueiras1,2

1Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain; 2CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain; 3Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa, USA; 4Laboratory of Metabolism, Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, Faculty of Medicine, Geneva, Switzerland; 5Department of Morphological Sciences, School of Medicine, Santiago de Compostela, Spain, 6Grupo Fisiopatología Endocrina, Complejo Hospitalario Universitario de Santiago-Instituto de Investigación Sanitaria (IDIS/SERGAS), Santiago de Compostela, Spain, 7Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA, 8Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.

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.

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