Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity

Summary: 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. Adi...

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Autores principales:	Masato Miyake, Jun Zhang, Akihiro Yasue, Satoshi Hisanaga, Kazue Tsugawa, Hiroshi Sakaue, Miho Oyadomari, Hiroshi Kiyonari, Seiichi Oyadomari
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Human metabolism Cell biology Science Q
Acceso en línea:	https://doaj.org/article/b4fe15ed228d472c8b907643f92e2fd9
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spelling	oai:doaj.org-article:b4fe15ed228d472c8b907643f92e2fd92021-11-28T04:36:37ZIntegrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity2589-004210.1016/j.isci.2021.103448https://doaj.org/article/b4fe15ed228d472c8b907643f92e2fd92021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S258900422101419Xhttps://doaj.org/toc/2589-0042Summary: 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.Masato MiyakeJun ZhangAkihiro YasueSatoshi HisanagaKazue TsugawaHiroshi SakaueMiho OyadomariHiroshi KiyonariSeiichi OyadomariElsevierarticleBiological sciencesHuman metabolismCell biologyScienceQENiScience, Vol 24, Iss 12, Pp 103448- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Human metabolism Cell biology Science Q
spellingShingle	Biological sciences Human metabolism Cell biology Science Q Masato Miyake Jun Zhang Akihiro Yasue Satoshi Hisanaga Kazue Tsugawa Hiroshi Sakaue Miho Oyadomari Hiroshi Kiyonari Seiichi Oyadomari Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity
description	Summary: 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.
format	article
author	Masato Miyake Jun Zhang Akihiro Yasue Satoshi Hisanaga Kazue Tsugawa Hiroshi Sakaue Miho Oyadomari Hiroshi Kiyonari Seiichi Oyadomari
author_facet	Masato Miyake Jun Zhang Akihiro Yasue Satoshi Hisanaga Kazue Tsugawa Hiroshi Sakaue Miho Oyadomari Hiroshi Kiyonari Seiichi Oyadomari
author_sort	Masato Miyake
title	Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity
title_short	Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity
title_full	Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity
title_fullStr	Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity
title_full_unstemmed	Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity
title_sort	integrated stress response regulates gdf15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/b4fe15ed228d472c8b907643f92e2fd9
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Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity

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