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The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community

Non-alcoholic fatty liver disease (NAFLD) is one of the primary causes of cirrhosis and a major risk factor for hepatocellular carcinoma and liver-related death. It has been correlated with changes in the gut microbiota, which promote its development by regulating insulin resistance, bile acid and c...

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Autores principales: Zhang, Qiang, Chen, Qiongyun, Yan, Changsheng, Niu, Chunyan, Zhou, Jingping, Liu, Jingjing, Song, Yang, Zhou, Fei, Fan, Yanyun, Ren, Jianlin, Xu, Hongzhi, Zhang, Bangzhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279660/
https://www.ncbi.nlm.nih.gov/pubmed/35844603
http://dx.doi.org/10.3389/fimmu.2022.931176
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author Zhang, Qiang
Chen, Qiongyun
Yan, Changsheng
Niu, Chunyan
Zhou, Jingping
Liu, Jingjing
Song, Yang
Zhou, Fei
Fan, Yanyun
Ren, Jianlin
Xu, Hongzhi
Zhang, Bangzhou
author_facet Zhang, Qiang
Chen, Qiongyun
Yan, Changsheng
Niu, Chunyan
Zhou, Jingping
Liu, Jingjing
Song, Yang
Zhou, Fei
Fan, Yanyun
Ren, Jianlin
Xu, Hongzhi
Zhang, Bangzhou
author_sort Zhang, Qiang
collection PubMed
description Non-alcoholic fatty liver disease (NAFLD) is one of the primary causes of cirrhosis and a major risk factor for hepatocellular carcinoma and liver-related death. It has been correlated with changes in the gut microbiota, which promote its development by regulating insulin resistance, bile acid and choline metabolism, and inflammation. Recent studies suggested a controversial role of the stimulator of interferon genes (STING) in the development of NAFLD. Here, we showed that as an immune regulator, STING aggravates the progression of NAFLD in diet-induced mice and correlated it with the changes in hepatic lipid metabolism and gut microbiota diversity. After feeding wild-type (WT) and STING deletion mice with a normal control diet (NCD) or a high-fat diet (HFD), the STING deletion mice showed decreased lipid accumulation and liver inflammation compared with WT mice fed the same diet. In addition, STING specifically produced this hepatoprotective effect by inhibiting the activation of CD8(+) T cells. The gut microbiota analysis revealed significant differences in intestinal bacteria between STING deletion mice and WT mice under the same diet and environmental conditions; moreover, differential bacterial genera were associated with altered metabolic phenotypes and involved in related metabolic pathways. Overall, our findings reveal the important regulatory role that STING plays in the progression of NAFLD. In addition, the change in intestinal microbiota diversity may be the contributing factor.
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spelling pubmed-92796602022-07-15 The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community Zhang, Qiang Chen, Qiongyun Yan, Changsheng Niu, Chunyan Zhou, Jingping Liu, Jingjing Song, Yang Zhou, Fei Fan, Yanyun Ren, Jianlin Xu, Hongzhi Zhang, Bangzhou Front Immunol Immunology Non-alcoholic fatty liver disease (NAFLD) is one of the primary causes of cirrhosis and a major risk factor for hepatocellular carcinoma and liver-related death. It has been correlated with changes in the gut microbiota, which promote its development by regulating insulin resistance, bile acid and choline metabolism, and inflammation. Recent studies suggested a controversial role of the stimulator of interferon genes (STING) in the development of NAFLD. Here, we showed that as an immune regulator, STING aggravates the progression of NAFLD in diet-induced mice and correlated it with the changes in hepatic lipid metabolism and gut microbiota diversity. After feeding wild-type (WT) and STING deletion mice with a normal control diet (NCD) or a high-fat diet (HFD), the STING deletion mice showed decreased lipid accumulation and liver inflammation compared with WT mice fed the same diet. In addition, STING specifically produced this hepatoprotective effect by inhibiting the activation of CD8(+) T cells. The gut microbiota analysis revealed significant differences in intestinal bacteria between STING deletion mice and WT mice under the same diet and environmental conditions; moreover, differential bacterial genera were associated with altered metabolic phenotypes and involved in related metabolic pathways. Overall, our findings reveal the important regulatory role that STING plays in the progression of NAFLD. In addition, the change in intestinal microbiota diversity may be the contributing factor. Frontiers Media S.A. 2022-06-30 /pmc/articles/PMC9279660/ /pubmed/35844603 http://dx.doi.org/10.3389/fimmu.2022.931176 Text en Copyright © 2022 Zhang, Chen, Yan, Niu, Zhou, Liu, Song, Zhou, Fan, Ren, Xu and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Qiang
Chen, Qiongyun
Yan, Changsheng
Niu, Chunyan
Zhou, Jingping
Liu, Jingjing
Song, Yang
Zhou, Fei
Fan, Yanyun
Ren, Jianlin
Xu, Hongzhi
Zhang, Bangzhou
The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community
title The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community
title_full The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community
title_fullStr The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community
title_full_unstemmed The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community
title_short The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community
title_sort absence of sting ameliorates non-alcoholic fatty liver disease and reforms gut bacterial community
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279660/
https://www.ncbi.nlm.nih.gov/pubmed/35844603
http://dx.doi.org/10.3389/fimmu.2022.931176
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