Melanocortin-3 receptor regulates the normal fasting response

Benjamin J Renquist, Jonathan G. Murphy, Emily A. Larson, Dawn Olsen, Robert F. Klein, Kate L J Ellacott, Roger D. Cone

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number23
DOIs
StatePublished - Jun 5 2012

Fingerprint

Receptor, Melanocortin, Type 3
Fasting
White Adipose Tissue
Phenotype
Hyperphagia
Cushing Syndrome
Lipolysis
Adiposity
Corticosterone
Nutritional Status
Bone Density
Triglycerides
Obesity
Salts
Hypertension
Inflammation
Food
Liver
Mouse Mc3r protein

Keywords

  • Corticotrophin-releasing hormone
  • Energy homeostasis
  • Hormone-sensitive lipase
  • Nonesterified fatty acid

ASJC Scopus subject areas

  • General

Cite this

Melanocortin-3 receptor regulates the normal fasting response. / Renquist, Benjamin J; Murphy, Jonathan G.; Larson, Emily A.; Olsen, Dawn; Klein, Robert F.; Ellacott, Kate L J; Cone, Roger D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 23, 05.06.2012.

Research output: Contribution to journalArticle

Renquist, Benjamin J ; Murphy, Jonathan G. ; Larson, Emily A. ; Olsen, Dawn ; Klein, Robert F. ; Ellacott, Kate L J ; Cone, Roger D. / Melanocortin-3 receptor regulates the normal fasting response. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 23.
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