Objectives: 

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide which is located in the lateral hypothalamus and regulate the energy balance. The MCH increases food intake and adiposity, so we sought to investigate the role of the MCH on adipocyte and hepatic metabolism.

Materials: 

We used three experimental groups: vehicle, MCH-ad libitum and MCH-pair fed (food restricted as the amount of the vehicle group). MCH were was chronically administered into the lateral ventricle intracerebroventricular using osmotic pumps that released the MCH for a week. To study whether the sympathetic nervous system mediates the actions of MCH on the adipocyte metabolism of white adipose tissue, deficient mice for the three beta-adrenergic receptors were used. To determine whether the central effect of MCH on the liver was mediated through the parasympathetic nervous system (PSNS), the vagus nerve was dissected a group of rats. We estereotaxically administered adenoviral particles overexpressing MCH receptors (MCH-R) into specific hypothalamic nuclei: lateral and arcuate (LHA, ARC). After treatment, animals were sacrificed and samples of serum, gonadal white adipose tissue and liver were collected. Tissues were analyzed to determine the expression of genes and proteins involved in lipid metabolism of liver and fat (quantitative RT-PCR, western blot).

Results: 

Activation of MCH-R increases fat deposition in WAT via the suppression of sympathetic traffic, whereas it promotes fat storage in the liver through the PSNS. In adipocytes, MCH induces metabolic pathways that promote lipid storage and decreases lipolysis; in the liver MCH triggers lipid accumulation and lipid uptake. The specific activation of MCH-R in the ARC and LHA during 1 week increaeses body weight gain and food intake, but the the diference in protein levels are in WAT on ARC and in liver on the LHA.

Conclusions: 

Central MCH system increases lipid storage via modulation of adipocyte and hepatic metabolism. Activation of MCH-R in the ARC control adipocyte lipd metabolism via a SNS-dependent mechanism while the activation of MCH-R in the LHA influences hepatic lipid metabolism through the PSNS.