Melanin-concentrating hormone (MCH) is a cyclic peptide highly conserved in vertebrates and was originally identified as a skin-paling factor in Teleosts. In fishes, MCH also participates in the regulation of the stress-response and feeding behaviour. Mammalian MCH is a hypothalamic neuropeptide that displays multiple functions, mostly controlling feeding behaviour and energy homeostasis. Transgenic mouse models and pharmacological studies have shown the importance of the MCH system as a potential target in the treatment of appetite disorders and obesity as well as anxiety and psychiatric diseases. Two G-proteincoupled receptors (GPCRs) binding MCH have been characterized so far. The first, named MCH-R1 and also called SLC1, was identified through reverse pharmacology strategies by several groups as a cognate receptor of MCH. This receptor is expressed at high levels in many brain areas of rodents and primates and is also expressed in peripheral organs, albeit at a lower rate. A second receptor, designated MCH-R2, exhibited 38% identity to MCH-R1 and was identified by sequence analysis of the human genome. Interestingly, although MCH-R2 orthologues were also found in fishes, dogs, ferrets and non-human primates, this MCH receptor gene appeared either lacking or non-functional in rodents and lagomorphs. Both receptors are class I GPCRs, whose main roles are to mediate the actions of peptides and neurotransmitters in the central nervous system. However, examples of action of MCH on neuronal and non-neuronal cells are emerging that illustrate novel MCH functions. In particular, the functionality of endogenously expressed MCH-R1 has been explored in human neuroblastoma cells, SK-N-SH and SH-SY5Y cells, and in non-neuronal cell types such as the ependymocytes. Indeed, we have identified mitogen-activated protein kinase (MAPK)-dependent or calcium-dependent signalling cascades that ultimately contributed to neurite outgrowth in neuroblastoma cells or to modulation of ciliary beating in ependymal cells. The putative role of MCH on cellular shaping and plasticity on one side and volume transmission on the other must be now considered.International Journal of Obesity Supplements (2014) 4, S31--S36; doi:10.1038/ijosup.2014.9Keywords: AROM gene; energy balance; feeding behaviour; melanin-concentrating hormone; MCH receptors; primate-specific PMCHL genes Melanin-concentrating hormone (MCH) is a cyclic peptide that was first isolated from salmon pituitary glands 1 and subsequently characterized in the rat hypothalamus.2 Brain and peripheral expression of MCH was then established in many mammalian species including humans (reviewed in Nahon et al.3 ). In the central nervous system, MCH mRNA and peptide syntheses were found predominantly in neurons of the lateral hypothalamus and zona incerta that projected throughout the brain 4,5 (Figure 1
12). The first receptor, named here MCH-R1, also called SLC1, was simultaneously identified through reverse pharmacology strategies by several groups as a cognate receptor of MCH. 13--16 ...