オオツキ　ミチオ   Ootsuki Michio   大月　道夫    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Adipocyte GR Inhibits Healthy Adipose Expansion Through Multiple Mechanisms in Cushing Syndrome
掲載誌名	正式名：Endocrinology 略　 称：Endocrinology ISSNコード：00137227/19457170
掲載区分	国外
巻・号・頁	160(3),pp.504-521
著者・共著者	Hayashi, R. Okuno, Y. Mukai, K. Kitamura, T. Hayakawa, T. Onodera, T. Murata, M. Fukuhara, A. Imamura, R. Miyagawa, Y. Nonomura, N. Otsuki, M. Shimomura, I.
担当区分	責任著者
発行年月	2019
概要	In Cushing syndrome, excessive glucocorticoids lead to metabolic disturbances, such as insulin resistance, adipocyte hypertrophy, and liver steatosis. In vitro experiments have highlighted the importance of adipocyte glucocorticoid receptor (GR), but its metabolic roles in vivo have not been fully elucidated in Cushing syndrome. In this study, using clinical samples from patients with Cushing syndrome and adipocyte-specific GR knockout (AGRKO) mice, we investigated the roles of adipocyte GR and its clinical relevance in Cushing syndrome. Under chronic treatment with corticosterone, AGRKO mice underwent healthy adipose expansion with diminished ectopic lipid deposition and improved insulin sensitivity. These changes were associated with Atgl-mediated lipolysis through a novel intronic glucocorticoid-responsive element. Additionally, integrated analysis with RNA sequencing of AGRKO mice and clinical samples revealed that healthy adipose expansion was associated with dysregulation of tissue remodeling, preadipocyte proliferation, and expression of the circadian gene. Thus, our study revealed the roles of adipocyte GR on healthy adipose expansion and its multiple mechanisms in Cushing syndrome.
DOI	10.1210/en.2018-01029
文献番号	30649271