title: Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass.
abstract: Genetic and pharmacological studies have defined a role for the melanocortin-4 receptor (Mc4r) in the regulation of energy homeostasis. The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown. We evaluated the potential role of Mc3r in energy homeostasis by studying Mc3r-deficient (Mc3r(-/-)) mice and compared the functions of Mc3r and Mc4r in mice deficient for both genes. The 4-6-month Mc3r-/- mice have increased fat mass, reduced lean mass and higher feed efficiency than wild-type littermates, despite being hypophagic and maintaining normal metabolic rates. (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia. Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels. Mice lacking both Mc3r and Mc4r become significantly heavier than Mc4r(-/-) mice. We conclude that Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis.
authors.affiliation: Department of Obesity Research, Merck Research Laboratories, Rahway, New Jersey, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Chen
authors.forename: D J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: M E
authors.initials: ME
authors.lastname: Trumbauer
authors.forename: E G
authors.initials: EG
authors.lastname: Frazier
authors.forename: X M
authors.initials: XM
authors.lastname: Guan
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: C I
authors.initials: CI
authors.lastname: Rosenblum
authors.forename: A
authors.initials: A
authors.lastname: Vongs
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.forename: J M
authors.initials: JM
authors.lastname: Metzger
authors.forename: A M
authors.initials: AM
authors.lastname: Strack
authors.forename: R E
authors.initials: RE
authors.lastname: Camacho
authors.forename: T N
authors.initials: TN
authors.lastname: Mellin
authors.forename: C N
authors.initials: CN
authors.lastname: Nunes
authors.forename: W
authors.initials: W
authors.lastname: Min
authors.forename: J
authors.initials: J
authors.lastname: Fisher
authors.forename: S
authors.initials: S
authors.lastname: Gopal-Truter
authors.forename: D E
authors.initials: DE
authors.lastname: MacIntyre
authors.forename: H Y
authors.initials: HY
authors.lastname: Chen
authors.forename: L H
authors.initials: LH
authors.lastname: Van der Ploeg
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D015139:Blotting, Southern; D001831:Body Temperature; D001835:Body Weight; D002151:Calorimetry; D003345:Corticosterone / Q000096:biosynthesis; D005247:Feeding Behavior; D005260:Female; D005838:Genotype; D005947:Glucose / Q000096:biosynthesis; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics; D017403:In Situ Hybridization; D007328:Insulin / Q000096:biosynthesis; D020738:Leptin / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009043:Motor Activity; D009765:Obesity / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D010641:Phenotype; D020033:Protein Isoforms; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D013974:Thyroxine / Q000096:biosynthesis; D013997:Time Factors; D014018:Tissue Distribution; D000521:alpha-MSH / Q000031:analogs & derivatives
chemical_list: D007328:Insulin; D020738:Leptin; D009842:Oligopeptides; D020033:Protein Isoforms; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D018000:Receptors, Peptide; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; D000521:alpha-MSH; D005947:Glucose; D013974:Thyroxine; D003345:Corticosterone