Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy
Abstract Background and aims Alcoholic fatty liver (AFL) is a liver disease caused by long-term excessive drinking and is characterized by hepatic steatosis. Understanding the regulatory mechanism of steatosis is essential for the treatment of AFL. Rev-erbα is a member of the Rev-erbs family of nucl...
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Online Access: | https://doi.org/10.1186/s13578-021-00622-4 |
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doaj-e177a0915ea04fd6aa80324be3d165cb2021-07-11T11:39:12ZengBMCCell & Bioscience2045-37012021-07-0111111510.1186/s13578-021-00622-4Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagyQingxue Liu0Lei Xu1Meifei Wu2Yiwen Zhou3Junfa Yang4Cheng Huang5Tao Xu6Jun Li7Lei Zhang8School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversitySchool of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversitySchool of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversitySchool of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversitySchool of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversitySchool of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversitySchool of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversitySchool of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversitySchool of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical UniversityAbstract Background and aims Alcoholic fatty liver (AFL) is a liver disease caused by long-term excessive drinking and is characterized by hepatic steatosis. Understanding the regulatory mechanism of steatosis is essential for the treatment of AFL. Rev-erbα is a member of the Rev-erbs family of nuclear receptors, playing an important role in regulating lipid metabolism. However, its functional role in AFL and its underlying mechanism remains unclear. Results Rev-erbα was upregulated in the liver of EtOH-fed mice and EtOH-treated L-02 cells. Further, Rev-erbα activation exacerbates steatosis in L-02 cells. Inhibition/downexpression of Rev-erbα improved steatosis. Mechanistically, autophagy activity was inhibited in vivo and vitro. Interestingly, inhibition/downexpression of Rev-erbα enhanced autophagy. Furthermore, silencing of Rev-erbα up-regulated the nuclear expression of Bmal1. Autophagy activity was inhibited and steatosis was deteriorated after EtOH-treated L-02 cells were cotransfected with Rev-erbα shRNA and Bmal1 siRNA. Conclusions Rev-erbα induces liver steatosis, which promotes the progression of AFL. Our study reveals a novel steatosis regulatory mechanism in AFL and suggest that Rev-erbα might be a potential therapeutic target for AFL.https://doi.org/10.1186/s13578-021-00622-4Rev-erbαAFLAutophagyBmal1Lysosome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qingxue Liu Lei Xu Meifei Wu Yiwen Zhou Junfa Yang Cheng Huang Tao Xu Jun Li Lei Zhang |
spellingShingle |
Qingxue Liu Lei Xu Meifei Wu Yiwen Zhou Junfa Yang Cheng Huang Tao Xu Jun Li Lei Zhang Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy Cell & Bioscience Rev-erbα AFL Autophagy Bmal1 Lysosome |
author_facet |
Qingxue Liu Lei Xu Meifei Wu Yiwen Zhou Junfa Yang Cheng Huang Tao Xu Jun Li Lei Zhang |
author_sort |
Qingxue Liu |
title |
Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy |
title_short |
Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy |
title_full |
Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy |
title_fullStr |
Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy |
title_full_unstemmed |
Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy |
title_sort |
rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy |
publisher |
BMC |
series |
Cell & Bioscience |
issn |
2045-3701 |
publishDate |
2021-07-01 |
description |
Abstract Background and aims Alcoholic fatty liver (AFL) is a liver disease caused by long-term excessive drinking and is characterized by hepatic steatosis. Understanding the regulatory mechanism of steatosis is essential for the treatment of AFL. Rev-erbα is a member of the Rev-erbs family of nuclear receptors, playing an important role in regulating lipid metabolism. However, its functional role in AFL and its underlying mechanism remains unclear. Results Rev-erbα was upregulated in the liver of EtOH-fed mice and EtOH-treated L-02 cells. Further, Rev-erbα activation exacerbates steatosis in L-02 cells. Inhibition/downexpression of Rev-erbα improved steatosis. Mechanistically, autophagy activity was inhibited in vivo and vitro. Interestingly, inhibition/downexpression of Rev-erbα enhanced autophagy. Furthermore, silencing of Rev-erbα up-regulated the nuclear expression of Bmal1. Autophagy activity was inhibited and steatosis was deteriorated after EtOH-treated L-02 cells were cotransfected with Rev-erbα shRNA and Bmal1 siRNA. Conclusions Rev-erbα induces liver steatosis, which promotes the progression of AFL. Our study reveals a novel steatosis regulatory mechanism in AFL and suggest that Rev-erbα might be a potential therapeutic target for AFL. |
topic |
Rev-erbα AFL Autophagy Bmal1 Lysosome |
url |
https://doi.org/10.1186/s13578-021-00622-4 |
work_keys_str_mv |
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1721308842564780032 |