Michio Otsuki
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title Adipocyte GR Inhibits Healthy Adipose Expansion Through Multiple Mechanisms in Cushing Syndrome
Journal Formal name：Endocrinology
Abbreviation：Endocrinology
ISSN code：00137227/19457170
Domestic / ForeginForegin
Volume, Issue, Page 160(3),pp.504-521
Author and coauthor 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.
Authorship Corresponding author
Publication date 2019
Summary 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
Document No. 30649271