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

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...

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Autores principales: Sakane, Sadatsugu, Hikita, Hayato, Shirai, Kumiko, Myojin, Yuta, Sasaki, Youichi, Kudo, Shinnosuke, Fukumoto, Kenji, Mizutani, Naoki, Tahata, Yuki, Makino, Yuki, Yamada, Ryoko, Kodama, Takahiro, Sakamori, Ryotaro, Tatsumi, Tomohide, Takehara, Tetsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551788/
https://www.ncbi.nlm.nih.gov/pubmed/34303881
http://dx.doi.org/10.1016/j.jcmgh.2021.07.008
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author Sakane, Sadatsugu
Hikita, Hayato
Shirai, Kumiko
Myojin, Yuta
Sasaki, Youichi
Kudo, Shinnosuke
Fukumoto, Kenji
Mizutani, Naoki
Tahata, Yuki
Makino, Yuki
Yamada, Ryoko
Kodama, Takahiro
Sakamori, Ryotaro
Tatsumi, Tomohide
Takehara, Tetsuo
author_facet Sakane, Sadatsugu
Hikita, Hayato
Shirai, Kumiko
Myojin, Yuta
Sasaki, Youichi
Kudo, Shinnosuke
Fukumoto, Kenji
Mizutani, Naoki
Tahata, Yuki
Makino, Yuki
Yamada, Ryoko
Kodama, Takahiro
Sakamori, Ryotaro
Tatsumi, Tomohide
Takehara, Tetsuo
author_sort Sakane, Sadatsugu
collection PubMed
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.
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spelling pubmed-85517882021-11-04 White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice Sakane, Sadatsugu Hikita, Hayato Shirai, Kumiko Myojin, Yuta Sasaki, Youichi Kudo, Shinnosuke Fukumoto, Kenji Mizutani, Naoki Tahata, Yuki Makino, Yuki Yamada, Ryoko Kodama, Takahiro Sakamori, Ryotaro Tatsumi, Tomohide Takehara, Tetsuo Cell Mol Gastroenterol Hepatol Original Research 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. Elsevier 2021-07-22 /pmc/articles/PMC8551788/ /pubmed/34303881 http://dx.doi.org/10.1016/j.jcmgh.2021.07.008 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Sakane, Sadatsugu
Hikita, Hayato
Shirai, Kumiko
Myojin, Yuta
Sasaki, Youichi
Kudo, Shinnosuke
Fukumoto, Kenji
Mizutani, Naoki
Tahata, Yuki
Makino, Yuki
Yamada, Ryoko
Kodama, Takahiro
Sakamori, Ryotaro
Tatsumi, Tomohide
Takehara, Tetsuo
White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice
title White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice
title_full White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice
title_fullStr White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice
title_full_unstemmed White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice
title_short White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice
title_sort white adipose tissue autophagy and adipose-liver crosstalk exacerbate nonalcoholic fatty liver disease in mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551788/
https://www.ncbi.nlm.nih.gov/pubmed/34303881
http://dx.doi.org/10.1016/j.jcmgh.2021.07.008
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