RESEARCH PAPER Mechanism of the anti-obesity effects induced by a novel Melanin-concentrating hormone 1-receptor antagonist in mice

Background and purpose: Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide expressed in the lateralhypothalamus that is involved in feeding and body weight regulation. Intracerebroventricular infusion of a peptidic MCH1receptor antagonist ameliorated obesity in murine models. Recently, small molecule MCH1 receptor antagonists have beendeveloped and characterized for the treatment of obesity. However, little is known of the mechanism of the anti-obesity effectsof MCH1 receptor antagonists.Experimental approach: To examine the mechanisms of action of the anti-obesity effect of MCH1 receptor antagonists moreprecisely, we conducted a pair-feeding study in mice with diet-induced obesity (DIO), chronically treated with an orally activeand highly selective MCH1 receptor antagonist and examined changes in mRNA expression levels in liver, brown and whiteadipose tissues. We also assessed the acute effects of the MCH1 receptor antagonist in energy expenditure under thermoneutralconditions.Key results: Treatment with the MCH1 receptor antagonist at 30 mg·kg