AgRP neuron-specific deletion of glucocorticoid receptor leads to increased energy expenditure and decreased body weight in female mice on a high-fat diet

Miyuki Shibata, Ryoichi Banno, Mariko Sugiyama, Takashi Tominaga, Takeshi Onoue, Taku Tsunekawa, Yoshinori Azuma, Daisuke Hagiwara, Wenjun Lu, Yoshihiro Ito, Motomitsu Goto, Hidetaka Suga, Yoshihisa Sugimura, Yutaka Oiso, Hiroshi Arima

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1457-1466
Number of pages10
JournalEndocrinology
Volume157
Issue number4
DOIs
Publication statusPublished - 01-04-2016

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Agouti-Related Protein
Glucocorticoid Receptors
High Fat Diet
Knockout Mice
Energy Metabolism
Body Weight
Neurons
Genotype
Eating
Diet
Arcuate Nucleus of Hypothalamus
Brown Adipose Tissue
Intra-Abdominal Fat
Adiposity
Neuropeptides
Oxygen Consumption
Glucocorticoids
Weight Gain
Adipose Tissue
Rodentia

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Shibata, Miyuki ; Banno, Ryoichi ; Sugiyama, Mariko ; Tominaga, Takashi ; Onoue, Takeshi ; Tsunekawa, Taku ; Azuma, Yoshinori ; Hagiwara, Daisuke ; Lu, Wenjun ; Ito, Yoshihiro ; Goto, Motomitsu ; Suga, Hidetaka ; Sugimura, Yoshihisa ; Oiso, Yutaka ; Arima, Hiroshi. / AgRP neuron-specific deletion of glucocorticoid receptor leads to increased energy expenditure and decreased body weight in female mice on a high-fat diet. In: Endocrinology. 2016 ; Vol. 157, No. 4. pp. 1457-1466.
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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 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.",
author = "Miyuki Shibata and Ryoichi Banno and Mariko Sugiyama and Takashi Tominaga and Takeshi Onoue and Taku Tsunekawa and Yoshinori Azuma and Daisuke Hagiwara and Wenjun Lu and Yoshihiro Ito and Motomitsu Goto and Hidetaka Suga and Yoshihisa Sugimura and Yutaka Oiso and Hiroshi Arima",
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Shibata, M, Banno, R, Sugiyama, M, Tominaga, T, Onoue, T, Tsunekawa, T, Azuma, Y, Hagiwara, D, Lu, W, Ito, Y, Goto, M, Suga, H, Sugimura, Y, Oiso, Y & Arima, H 2016, '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, vol. 157, no. 4, pp. 1457-1466. https://doi.org/10.1210/en.2015-1430

AgRP neuron-specific deletion of glucocorticoid receptor leads to increased energy expenditure and decreased body weight in female mice on a high-fat diet. / Shibata, Miyuki; Banno, Ryoichi; Sugiyama, Mariko; Tominaga, Takashi; Onoue, Takeshi; Tsunekawa, Taku; Azuma, Yoshinori; Hagiwara, Daisuke; Lu, Wenjun; Ito, Yoshihiro; Goto, Motomitsu; Suga, Hidetaka; Sugimura, Yoshihisa; Oiso, Yutaka; Arima, Hiroshi.

In: Endocrinology, Vol. 157, No. 4, 01.04.2016, p. 1457-1466.

Research output: Contribution to journalArticle

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

PY - 2016/4/1

Y1 - 2016/4/1

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.

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