title: AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet.
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.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Banno
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tominaga
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Onoue
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Tsunekawa
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Azuma
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Motomitsu
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Suga
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D011965:Receptors, Glucocorticoid