Chapter II The melanin-concentrating hormone

The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis

“…As illustrated in Fig. 3, MCH-R1 mRNA and protein are widely distributed in the rat and mouse brain, in agreement with the major projection sites of MCH neurons [138,139] reviewed in [32]. In the hypothalamus, a very high expression of MCH-R1 is found in ventromedial and dorsomedial nuclei, both major regions that regulate feeding.…”

“…Melanin-concentrating hormone (MCH) is a cyclic peptide that was found expressed in the brain of many vertebrate taxa, the most well-established structural, expression and functional studies being in teleosts and mammals (reviewed in [29][30][31][32]). The peptide was initially discovered, and incidently named, on the basis of its telling pigment aggregation property in salmon fish skin, opposing the pigmentary dispersing effects of α-MSH.…”

“…A second MCH receptor, called MCH-R2, was initially identified in humans by in silico screening (reviewed in [36,135,136]) and more recently in fishes [141] but is apparently lacking in rats and mice [142]. MCH-R2 displays only 38% sequence identity to MCH-R1 and exhibits a partly distinct expression profile in the human brain and peripheral tissues (reviewed in [32]). Furthermore, analysis of the signaling profile of human MCH-R2 in heterologous cell lines suggests that this receptor couples quite exclusively to Gαq protein to increase intracellular Ca 2+ levels.…”

“…Furthermore, the melanocortins form part of a larger peptide family, the melanotropins whose members all exhibit strong action on pigmentation, mainly in lower vertebrates [28]. Among these, there is melaninconcentrating hormone (MCH), a functional antagonist of α-MSH on melanophores, which has a very particular history at the early times, punctuated by long periods of limited studies, interrupted by short phases of intense investigations, when peptide purification or precursorencoding mRNA cloning data were reported (reviewed in [29][30][31][32]). The interest in MCH rapidly increased after 1996 because of the first demonstration that this peptide may induce food intake after central injections [33] and that its gene expression may be modulated by fasting in normal rats [34] or in hypoleptinemic ob/ob mice [33].…”

The Role of Melanin-Concentrating Hormone and Its Receptors in Energy Homeostasis

“…However, in four reports, the MCHR1-specific efficacy of antagonists was confirmed, since the antagonists lacked efficacy in DIO Mchr1 KO mice, but they showed body-weight loss in DIO wild-type mice (Gehlert et al, 2009; Della-Zuana et al, 2012; Mashiko et al, 2005; Mihalic et al, 2012). Further support for an MCHR1 mechanism based-weight loss has been reported for three compounds, for which efficacy was correlated with brain MCHR1 receptor occupancy (Hervieu et al, 2003; Kowalski et al, 2006; Ito et al, 2009). …”