White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary

Background & Aims: Although nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity, the role of adipose tissue in NAFLD is not well-understood. Because autophagy has been reported to be involved in the degradation of lipid droplets, we investigated the role of adipose ti...

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Autores principales:	Sadatsugu Sakane, Hayato Hikita, Kumiko Shirai, Yuta Myojin, Youichi Sasaki, Shinnosuke Kudo, Kenji Fukumoto, Naoki Mizutani, Yuki Tahata, Yuki Makino, Ryoko Yamada, Takahiro Kodama, Ryotaro Sakamori, Tomohide Tatsumi, Tetsuo Takehara
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Nonalcoholic Steatohepatitis Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/6c57edd099aa446b96cd53391b486ebb
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spelling	oai:doaj.org-article:6c57edd099aa446b96cd53391b486ebb2021-11-12T04:39:06ZWhite Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary2352-345X10.1016/j.jcmgh.2021.07.008https://doaj.org/article/6c57edd099aa446b96cd53391b486ebb2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352345X21001533https://doaj.org/toc/2352-345XBackground & Aims: Although nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity, the role of adipose tissue in NAFLD is not well-understood. Because autophagy has been reported to be involved in the degradation of lipid droplets, we investigated the role of adipose tissue autophagy in the liver pathogenesis of NAFLD. Methods: C57BL/6J mice and adipocyte-specific Atg7-knockout mice (Adipoq-Atg7 KO mice) were fed a high-fat diet (HFD). Results: HFD feeding for up to 4 months increased both inguinal and epididymal white adipose tissue (iWAT and eWAT, respectively; the former represents subcutaneous fat, and the latter represents visceral fat) in mice. After HFD feeding, autophagy flux in both types of white adipose tissue was increased, and the levels of Rubicon, a negative autophagy regulator, were decreased, suggesting autophagy promotion. Adipoq-Atg7 KO mice exhibited suppressed autophagy in both iWAT and eWAT. Adipocyte-specific Atg7 KO enhanced HFD-induced iWAT hypertrophy. On the other hand, eWAT levels in Adipoq-Atg7 KO mice were increased after 1 month of HFD feeding but decreased after 4 months of HFD feeding compared with those in wild-type controls. Cleaved caspase 3 and JNK pathway protein expression in eWAT was increased without cytokine elevation in Adipoq-Atg7 KO mice fed an HFD compared with wild-type mice fed an HFD. Adipocyte-specific Atg7 KO decreased serum free fatty acid levels and ameliorated HFD-induced steatosis, liver inflammation, and fibrosis. Conclusions: Autophagy was enhanced in the white adipose tissues of mice fed an HFD. Autophagy inhibition in white adipose tissues ameliorated the liver pathology of NAFLD via adipose-liver crosstalk.Sadatsugu SakaneHayato HikitaKumiko ShiraiYuta MyojinYouichi SasakiShinnosuke KudoKenji FukumotoNaoki MizutaniYuki TahataYuki MakinoRyoko YamadaTakahiro KodamaRyotaro SakamoriTomohide TatsumiTetsuo TakeharaElsevierarticleNonalcoholic SteatohepatitisDiseases of the digestive system. GastroenterologyRC799-869ENCellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 5, Pp 1683-1699 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nonalcoholic Steatohepatitis Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Nonalcoholic Steatohepatitis Diseases of the digestive system. Gastroenterology RC799-869 Sadatsugu Sakane Hayato Hikita Kumiko Shirai Yuta Myojin Youichi Sasaki Shinnosuke Kudo Kenji Fukumoto Naoki Mizutani Yuki Tahata Yuki Makino Ryoko Yamada Takahiro Kodama Ryotaro Sakamori Tomohide Tatsumi Tetsuo Takehara White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary
description	Background & Aims: Although nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity, the role of adipose tissue in NAFLD is not well-understood. Because autophagy has been reported to be involved in the degradation of lipid droplets, we investigated the role of adipose tissue autophagy in the liver pathogenesis of NAFLD. Methods: C57BL/6J mice and adipocyte-specific Atg7-knockout mice (Adipoq-Atg7 KO mice) were fed a high-fat diet (HFD). Results: HFD feeding for up to 4 months increased both inguinal and epididymal white adipose tissue (iWAT and eWAT, respectively; the former represents subcutaneous fat, and the latter represents visceral fat) in mice. After HFD feeding, autophagy flux in both types of white adipose tissue was increased, and the levels of Rubicon, a negative autophagy regulator, were decreased, suggesting autophagy promotion. Adipoq-Atg7 KO mice exhibited suppressed autophagy in both iWAT and eWAT. Adipocyte-specific Atg7 KO enhanced HFD-induced iWAT hypertrophy. On the other hand, eWAT levels in Adipoq-Atg7 KO mice were increased after 1 month of HFD feeding but decreased after 4 months of HFD feeding compared with those in wild-type controls. Cleaved caspase 3 and JNK pathway protein expression in eWAT was increased without cytokine elevation in Adipoq-Atg7 KO mice fed an HFD compared with wild-type mice fed an HFD. Adipocyte-specific Atg7 KO decreased serum free fatty acid levels and ameliorated HFD-induced steatosis, liver inflammation, and fibrosis. Conclusions: Autophagy was enhanced in the white adipose tissues of mice fed an HFD. Autophagy inhibition in white adipose tissues ameliorated the liver pathology of NAFLD via adipose-liver crosstalk.
format	article
author	Sadatsugu Sakane Hayato Hikita Kumiko Shirai Yuta Myojin Youichi Sasaki Shinnosuke Kudo Kenji Fukumoto Naoki Mizutani Yuki Tahata Yuki Makino Ryoko Yamada Takahiro Kodama Ryotaro Sakamori Tomohide Tatsumi Tetsuo Takehara
author_facet	Sadatsugu Sakane Hayato Hikita Kumiko Shirai Yuta Myojin Youichi Sasaki Shinnosuke Kudo Kenji Fukumoto Naoki Mizutani Yuki Tahata Yuki Makino Ryoko Yamada Takahiro Kodama Ryotaro Sakamori Tomohide Tatsumi Tetsuo Takehara
author_sort	Sadatsugu Sakane
title	White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary
title_short	White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary
title_full	White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary
title_fullStr	White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary
title_full_unstemmed	White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary
title_sort	white adipose tissue autophagy and adipose-liver crosstalk exacerbate nonalcoholic fatty liver disease in micesummary
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/6c57edd099aa446b96cd53391b486ebb
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White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in MiceSummary

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