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Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α

Rationale: Over-nutrition will lead to overexpression of PRMT1 but protein hypomethylation is observed in the liver of obese subjects. The dynamic alteration of the expression and methyltransferase activity of PRMT1 in the progression of fatty liver diseases remains elusive. Methods: We used recombi...

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Autores principales: Xu, Lu, Huang, Zhe, Lo, Tak-ho, Lee, Jimmy Tsz Hang, Yang, Ranyao, Yan, Xingqun, Ye, Dewei, Xu, Aimin, Wong, Chi-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965489/
https://www.ncbi.nlm.nih.gov/pubmed/35401831
http://dx.doi.org/10.7150/thno.63824
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author Xu, Lu
Huang, Zhe
Lo, Tak-ho
Lee, Jimmy Tsz Hang
Yang, Ranyao
Yan, Xingqun
Ye, Dewei
Xu, Aimin
Wong, Chi-Ming
author_facet Xu, Lu
Huang, Zhe
Lo, Tak-ho
Lee, Jimmy Tsz Hang
Yang, Ranyao
Yan, Xingqun
Ye, Dewei
Xu, Aimin
Wong, Chi-Ming
author_sort Xu, Lu
collection PubMed
description Rationale: Over-nutrition will lead to overexpression of PRMT1 but protein hypomethylation is observed in the liver of obese subjects. The dynamic alteration of the expression and methyltransferase activity of PRMT1 in the progression of fatty liver diseases remains elusive. Methods: We used recombinant adeno-associated virus-mediated gene delivery system to manipulate the hepatic PRMT1 expression level in diet-induced obese mice to investigate the role of PRMT1 in hepatic steatosis. We further utilized a cohort of obese humans with biopsy-proven nonalcoholic fatty liver disease to support our observations in mouse model. Results: We demonstrated that knockdown of PRMT1 promoted steatosis development in liver of high-fat diet (HFD) fed mice. Over-expression of wild-type PRMT1, but not methyltransferase-defective mutant PRMT1(G80R), could alleviate diet-induced hepatic steatosis. The observation is conserved in the specimens of obese humans with biopsy-proven nonalcoholic fatty liver disease. Mechanistically, methyltransferase activity of PRMT1 was required to induce PGC-1α mRNA expression via recruitment of HNF-4α to the promoter of PGC-1α, and hence attenuated HFD-induced hepatic steatosis by enhancing PGC-1α-mediated fatty acid oxidation. Conclusions: Our results identify that activation of the PRMT1/HNF-4α/PGC-1α signaling is a potential therapeutic strategy for combating non-alcoholic fatty liver disease of obese subjects.
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spelling pubmed-89654892022-04-07 Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α Xu, Lu Huang, Zhe Lo, Tak-ho Lee, Jimmy Tsz Hang Yang, Ranyao Yan, Xingqun Ye, Dewei Xu, Aimin Wong, Chi-Ming Theranostics Research Paper Rationale: Over-nutrition will lead to overexpression of PRMT1 but protein hypomethylation is observed in the liver of obese subjects. The dynamic alteration of the expression and methyltransferase activity of PRMT1 in the progression of fatty liver diseases remains elusive. Methods: We used recombinant adeno-associated virus-mediated gene delivery system to manipulate the hepatic PRMT1 expression level in diet-induced obese mice to investigate the role of PRMT1 in hepatic steatosis. We further utilized a cohort of obese humans with biopsy-proven nonalcoholic fatty liver disease to support our observations in mouse model. Results: We demonstrated that knockdown of PRMT1 promoted steatosis development in liver of high-fat diet (HFD) fed mice. Over-expression of wild-type PRMT1, but not methyltransferase-defective mutant PRMT1(G80R), could alleviate diet-induced hepatic steatosis. The observation is conserved in the specimens of obese humans with biopsy-proven nonalcoholic fatty liver disease. Mechanistically, methyltransferase activity of PRMT1 was required to induce PGC-1α mRNA expression via recruitment of HNF-4α to the promoter of PGC-1α, and hence attenuated HFD-induced hepatic steatosis by enhancing PGC-1α-mediated fatty acid oxidation. Conclusions: Our results identify that activation of the PRMT1/HNF-4α/PGC-1α signaling is a potential therapeutic strategy for combating non-alcoholic fatty liver disease of obese subjects. Ivyspring International Publisher 2022-02-28 /pmc/articles/PMC8965489/ /pubmed/35401831 http://dx.doi.org/10.7150/thno.63824 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Xu, Lu
Huang, Zhe
Lo, Tak-ho
Lee, Jimmy Tsz Hang
Yang, Ranyao
Yan, Xingqun
Ye, Dewei
Xu, Aimin
Wong, Chi-Ming
Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α
title Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α
title_full Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α
title_fullStr Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α
title_full_unstemmed Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α
title_short Hepatic PRMT1 ameliorates diet-induced hepatic steatosis via induction of PGC1α
title_sort hepatic prmt1 ameliorates diet-induced hepatic steatosis via induction of pgc1α
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965489/
https://www.ncbi.nlm.nih.gov/pubmed/35401831
http://dx.doi.org/10.7150/thno.63824
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