AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet

Endocrinology
Miyuki ShibataHiroshi Arima

Abstract

Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 ...Continue Reading

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Citations

Apr 30, 2017·The Journal of Endocrinology·Luba SominskySarah J Spencer
Oct 14, 2017·Endocrinology·Shannon Whirledge, Donald B DeFranco
Nov 11, 2017·Frontiers in Endocrinology·Ilvana ZikoSarah J Spencer
Jan 1, 2019·The Journal of Clinical Endocrinology and Metabolism·Gabrielle Page-WilsonSharon L Wardlaw
Sep 29, 2019·Journal of Neurochemistry·Rachel E LackieMarco A M Prado
Dec 16, 2019·The Journal of Clinical Endocrinology and Metabolism·Sunil K PanigrahiSharon L Wardlaw
Feb 22, 2017·The Journal of Clinical Investigation·Yong XuJoel K Elmquist
Jun 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rachel J PerryGerald I Shulman

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