Melanocortin-3 Receptor Regulates the Normal Fasting Response

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 May 11

PMID 22573815

Citations 52

Authors

Benjamin J Renquist

Jonathan G Murphy

Emily A Larson

Dawn Olsen

Robert F Klein

Kate L J Ellacott

Roger D Cone

Affiliations

Soon will be listed here.

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.

Citing Articles

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