TY - JOUR
T1 - AgRP neuron-specific deletion of glucocorticoid receptor leads to increased energy expenditure and decreased body weight in female mice on a high-fat diet
AU - Shibata, Miyuki
AU - Banno, Ryoichi
AU - Sugiyama, Mariko
AU - Tominaga, Takashi
AU - Onoue, Takeshi
AU - Tsunekawa, Taku
AU - Azuma, Yoshinori
AU - Hagiwara, Daisuke
AU - Lu, Wenjun
AU - Ito, Yoshihiro
AU - Goto, Motomitsu
AU - Suga, Hidetaka
AU - Sugimura, Yoshihisa
AU - Oiso, Yutaka
AU - Arima, Hiroshi
N1 - Publisher Copyright:
Copyright © 2016 by the Endocrine Society.
PY - 2016/4
Y1 - 2016/4
N2 - 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 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.
AB - 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 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.
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U2 - 10.1210/en.2015-1430
DO - 10.1210/en.2015-1430
M3 - Article
C2 - 26889940
AN - SCOPUS:84964414073
SN - 0013-7227
VL - 157
SP - 1457
EP - 1466
JO - Endocrinology
JF - Endocrinology
IS - 4
ER -