TY - JOUR
T1 - Melanocortin-3 receptor regulates the normal fasting response
AU - Renquist, Benjamin J.
AU - Murphy, Jonathan G.
AU - Larson, Emily A.
AU - Olsen, Dawn
AU - Klein, Robert F.
AU - Ellacott, Kate L.J.
AU - Cone, Roger D.
PY - 2012/6/5
Y1 - 2012/6/5
N2 - 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.
AB - 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.
KW - Corticotrophin-releasing hormone
KW - Energy homeostasis
KW - Hormone-sensitive lipase
KW - Nonesterified fatty acid
UR - http://www.scopus.com/inward/record.url?scp=84861905118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861905118&partnerID=8YFLogxK
U2 - 10.1073/pnas.1201994109
DO - 10.1073/pnas.1201994109
M3 - Article
C2 - 22573815
AN - SCOPUS:84861905118
SN - 0027-8424
VL - 109
SP - E1489-E1498
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -