title: Melanocortin-3 receptor regulates the normal fasting response.
abstract: The melanocortin-3 receptor-deficient (MC3-R(-/-)) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R(-/-) mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R(-/-) mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Renquist
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Murphy
authors.forename: Emily A
authors.initials: EA
authors.lastname: Larson
authors.forename: Dawn
authors.initials: D
authors.lastname: Olsen
authors.forename: Robert F
authors.initials: RF
authors.lastname: Klein
authors.forename: Kate L J
authors.initials: KL
authors.lastname: Ellacott
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cone
mesh_terms: D015502:Absorptiometry, Photon; D052436:Adipose Tissue, White / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000311:Adrenal Glands / Q000166:cytology; D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D001823:Body Composition / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005215:Fasting / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008066:Lipolysis / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010913:Pituitary-Adrenal System / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D044104:Receptor, Melanocortin, Type 3 / Q000172:deficiency / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D044104:Receptor, Melanocortin, Type 3; D014280:Triglycerides; D003345:Corticosterone