Multifaceted actions of melanin-concentrating hormone on mammalian energy homeostasis

Abstract

Melanin-concentrating hormone (MCH) is a small cyclic peptide expressed in all mammals, mainly in the hypothalamus. MCH acts as a robust integrator of several physiological functions and has crucial roles in the regulation of sleep–wake rhythms, feeding behaviour and metabolism. MCH signalling has a very broad endocrine context and is involved in physiological functions and emotional states associated with metabolism, such as reproduction, anxiety, depression, sleep and circadian rhythms. MCH mediates its functions through two receptors (MCHR1 and MCHR2), of which only MCHR1 is common to all mammals. Owing to the wide variety of MCH downstream signalling pathways, MCHR1 agonists and antagonists have great potential as tools for the directed management of energy balance disorders and associated metabolic complications, and translational strategies using these compounds hold promise for the development of novel treatments for obesity. This Review provides an overview of the numerous roles of MCH in energy and glucose homeostasis, as well as in regulation of the mesolimbic dopaminergic circuits that encode the hedonic component of food intake. Melanin-concentrating hormone (MCH) integrates physiological functions and mood states associated with energy and glucose homeostasis. In this Review, Al-Massadi et al. describe how MCH regulates the hedonic component of food intake and discuss its potential as a therapeutic target. Melanin-concentrating hormone (MCH) is a highly conserved, 19 amino acid peptide, and MCH-immunoreactive neuronal cell bodies exist in a wide range of species (fish, reptiles, birds and mammals). MCH is found mainly in the lateral hypothalamic area and zona incerta, and it exerts its effects through MCH receptor 1 (MCHR1) and MCHR2 in mammals (except rodents and lagomorphs). In addition to stimulating food intake via homeostatic and hedonic pathways, MCH reduces energy expenditure and locomotor activity, and induces adiposity, weight gain, glucose intolerance and peripheral lipid storage. MCH is not a meal-initiation hormone; instead, MCH signalling amplifies food intake after feeding initiation, thereby increasing sucrose and glucose intake. MCH neurons are active during sleep and mostly silent during wakefulness; however, MCH neurons can also be active during wakefulness. Melanin-concentrating hormone (MCH) is a highly conserved, 19 amino acid peptide, and MCH-immunoreactive neuronal cell bodies exist in a wide range of species (fish, reptiles, birds and mammals). MCH is found mainly in the lateral hypothalamic area and zona incerta, and it exerts its effects through MCH receptor 1 (MCHR1) and MCHR2 in mammals (except rodents and lagomorphs). In addition to stimulating food intake via homeostatic and hedonic pathways, MCH reduces energy expenditure and locomotor activity, and induces adiposity, weight gain, glucose intolerance and peripheral lipid storage. MCH is not a meal-initiation hormone; instead, MCH signalling amplifies food intake after feeding initiation, thereby increasing sucrose and glucose intake. MCH neurons are active during sleep and mostly silent during wakefulness; however, MCH neurons can also be active during wakefulness.