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Lei Zhang
School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9778-5726
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AFL is a liver disease caused by long-term excessive drinking, it is characterized by steatosis. Understanding the regulatory mechanism of steatosis is crucial for the treatment of AFL. Rev-erbα has been implicated in regulation of lipid metabolism. However, the role and the underlying mechanisms of Rev-erbα in AFL remains unknown. In this study, the antagonists or agonists of Rev-erbα as well as Rev-erbα shRNA were applied in vitro and vivo. Triglyceride and lipid droplets accumulation were measured by using TG kit and ORO staining. Lipid synthesis related factor Srebp1c and lipid β-oxidation regulatory factor Pparα were measured by using Western blot, qRT-PCR and immunohistochemistry analysis. Autophagy activity was measured by western blot and electron microscope, and lysosomal probe was used to labeled lysosomal acidity. We observed that the expression of Rev-erbα was significantly increased in vivo and vitro, and Rev-erbα activation mediated steatosis in L-02 cells. then, inhibition/down-expression of Rev-erbα improved the triglyceride and lipid droplets accumulation and the abnormal expression of Pparα and Srebp1c through enhancing the autophagy activity. Furthermore, down-expression of Rev-erbα up-regulated the nuclear expression of Bmal1, which regulated the autophagy activity in vitro. Collectively, these findings indicate that Rev-erbα induces liver steatosis and leads to 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.
Keywords
Rev-erbα, AFL, Autophagy, Bmal1, Lysosome
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See the published version of this preprint at Cell & Bioscience.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Lei Zhang
School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9778-5726
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Cell & Bioscience.
Version 1
Posted 29 Jan, 2021
No community comments so far
Editor assigned
On 24 Jan, 2021
Editor invited
On 24 Jan, 2021
Submission checks complete
On 23 Jan, 2021
First submitted
On 21 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
General Cell Biology & Physiology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Cell & Bioscience.
AFL is a liver disease caused by long-term excessive drinking, it is characterized by steatosis. Understanding the regulatory mechanism of steatosis is crucial for the treatment of AFL. Rev-erbα has been implicated in regulation of lipid metabolism. However, the role and the underlying mechanisms of Rev-erbα in AFL remains unknown. In this study, the antagonists or agonists of Rev-erbα as well as Rev-erbα shRNA were applied in vitro and vivo. Triglyceride and lipid droplets accumulation were measured by using TG kit and ORO staining. Lipid synthesis related factor Srebp1c and lipid β-oxidation regulatory factor Pparα were measured by using Western blot, qRT-PCR and immunohistochemistry analysis. Autophagy activity was measured by western blot and electron microscope, and lysosomal probe was used to labeled lysosomal acidity. We observed that the expression of Rev-erbα was significantly increased in vivo and vitro, and Rev-erbα activation mediated steatosis in L-02 cells. then, inhibition/down-expression of Rev-erbα improved the triglyceride and lipid droplets accumulation and the abnormal expression of Pparα and Srebp1c through enhancing the autophagy activity. Furthermore, down-expression of Rev-erbα up-regulated the nuclear expression of Bmal1, which regulated the autophagy activity in vitro. Collectively, these findings indicate that Rev-erbα induces liver steatosis and leads to 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
The full text of this article is available to read as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
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