Melanocortin-3 receptor regulates the normal fasting response.

Renquist BJ, Murphy JG, Larson EA, Olsen D, Klein RF, Ellacott KL, Cone RD
Proc Natl Acad Sci U S A. 2012 109 (23): E1489-98

PMID: 22573815 · PMCID: PMC3384161 · DOI:10.1073/pnas.1201994109

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.

MeSH Terms (24)

Absorptiometry, Photon Adipose Tissue, White Adiposity Adrenal Glands Analysis of Variance Animals Biomechanical Phenomena Blotting, Western Body Composition Corticosterone Energy Metabolism Fasting Hypothalamo-Hypophyseal System Immunohistochemistry In Situ Hybridization Lipolysis Liver Male Mice Mice, Knockout Pituitary-Adrenal System Real-Time Polymerase Chain Reaction Receptor, Melanocortin, Type 3 Triglycerides

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