title: Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism.
abstract: Melanin-concentrating hormone (MCH) is a cyclic 19-aa hypothalamic neuropeptide derived from a larger prohormone precursor of MCH (Pmch), which also encodes neuropeptide EI (NEI) and neuropeptide GE (NGE). Pmch-deficient (Pmch-/-) mice are lean, hypophagic, and have an increased metabolic rate. Transgenic mice overexpressing Pmch are hyperphagic and develop mild obesity. Consequently, MCH has been implicated in the regulation of energy homeostasis. The MCH 1 receptor (MCH1R) is one of two recently identified G protein-coupled receptors believed to be responsible for the actions of MCH. We evaluated the physiological role of MCH1R by generating MCH1R-deficient (Mch1r-/-) mice. Mch1r-/- mice have normal body weights, yet are lean and have reduced fat mass. Surprisingly, Mch1r-/- mice are hyperphagic when maintained on regular chow, and their leanness is a consequence of hyperactivity and altered metabolism. Consistent with the hyperactivity, Mch1r-/- mice are less susceptible to diet-induced obesity. Importantly, chronic central infusions of MCH induce hyperphagia and mild obesity in wild-type mice, but not in Mch1r-/- mice. We conclude that MCH1R is a physiologically relevant MCH receptor in mice that plays a role in energy homeostasis through multiple actions on locomotor activity, metabolism, appetite, and neuroendocrine function.
authors.affiliation: Department of Obesity Research, Animal Pharmacology, and Comparative Medicine, Merck Research Laboratories, Rahway, NJ 07065, USA. donald_marsh@merck.com
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: Drew T
authors.initials: DT
authors.lastname: Weingarth
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Novi
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chen
authors.forename: Myrna E
authors.initials: ME
authors.lastname: Trumbauer
authors.forename: Airu S
authors.initials: AS
authors.lastname: Chen
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Guan
authors.forename: Michael M
authors.initials: MM
authors.lastname: Jiang
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.forename: Ramon E
authors.initials: RE
authors.lastname: Camacho
authors.forename: Zhu
authors.initials: Z
authors.lastname: Shen
authors.forename: Easter G
authors.initials: EG
authors.lastname: Frazier
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Metzger
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Kuca
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Shearman
authors.forename: Shobhna
authors.initials: S
authors.lastname: Gopal-Truter
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: MacNeil
authors.forename: Alison M
authors.initials: AM
authors.lastname: Strack
authors.forename: D Euan
authors.initials: DE
authors.lastname: MacIntyre
authors.forename: Lex H T
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: Su
authors.initials: S
authors.lastname: Qian
mesh_terms: D054369:Agouti-Related Protein; D000818:Animals; D019167:Appetite Stimulants / Q000008:administration & dosage; D001823:Body Composition; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004041:Dietary Fats / Q000009:adverse effects; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D006128:Growth; D006948:Hyperkinesis / Q000209:etiology / Q000378:metabolism*; D006963:Hyperphagia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009478:Neuropeptide Y / Q000008:administration & dosage; D009490:Neurosecretory Systems; D009765:Obesity / Q000139:chemically induced; D010446:Peptide Fragments / Q000008:administration & dosage; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000502:physiology*
chemical_list: D054369:Agouti-Related Protein; D019167:Appetite Stimulants; D004041:Dietary Fats; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011979:Receptors, Pituitary Hormone; C411703:agouti-related protein-(83-132); C092274:melanin-concentrating hormone receptor; D003346:Corticotropin-Releasing Hormone