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ID 116908
著者
Zhang, Jun Tokushima University|ER Stress Research Institute
Hisanaga, Satoshi Tokushima University|Kumamoto University
Tsugawa, Kazue Tokushima University
Kiyonari, Hiroshi RIKEN
親泊, 政一 Tokushima University|ER Stress Research Institute 徳島大学 教育研究者総覧 KAKEN研究者をさがす
資料タイプ
学術雑誌論文
抄録
The eIF2α phosphorylation-dependent integrated stress response (ISR) is a signaling pathway that maintains homeostasis in mammalian cells exposed to various stresses. Here, ISR activation in adipocytes improves obesity and diabetes by regulating appetite in a non-cell-autonomous manner. Adipocyte-specific ISR activation using transgenic mice decreases body weight and improves glucose tolerance and obesity induced by a high-fat diet (HFD) via preferential inhibition of HFD intake. The transcriptome analysis of ISR-activated adipose tissue reveals that growth differentiation factor 15 (GDF15) expression is induced by the ISR through the direct regulation of the transcription factors ATF4 and DDIT3. Deficiency in the GDF15 receptor GFRAL abolishes the adipocyte ISR-dependent preferential inhibition of HFD intake and the anti-obesity effects. Pharmacologically, 10(E), 12(Z)-octadecadienoic acid induces ISR-dependent GDF15 expression in adipocytes and decreases the intake of the HFD. Based on our findings the specific activation of the ISR in adipocytes controls the non-cell-autonomous regulation of appetite.
掲載誌名
iScience
ISSN
25890042
出版者
Elsevier
24
12
開始ページ
103448
発行日
2021-12-17
権利情報
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所
病院
医学系