Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1

Nonalcoholic fatty liver disease (NAFLD) is recognized as a metabolic disease characterized by hepatic steatosis. Despite the growing burden of NAFLD, approved pharmacological treatment is lacking. As an inhibitor of androgen receptor (AR), EPI-001 is being explored for the treatment of prostate can...

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Autores principales: Wang, Shuqin, Li, Xue, Xu, Weizhe, Gao, Jing, Wang, Yin, Jia, Xiaoyuan, Li, Gongchu, Pan, Qiuwei, Chen, Kan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785868/
https://www.ncbi.nlm.nih.gov/pubmed/36555703
http://dx.doi.org/10.3390/ijms232416063
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author Wang, Shuqin
Li, Xue
Xu, Weizhe
Gao, Jing
Wang, Yin
Jia, Xiaoyuan
Li, Gongchu
Pan, Qiuwei
Chen, Kan
author_facet Wang, Shuqin
Li, Xue
Xu, Weizhe
Gao, Jing
Wang, Yin
Jia, Xiaoyuan
Li, Gongchu
Pan, Qiuwei
Chen, Kan
author_sort Wang, Shuqin
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD) is recognized as a metabolic disease characterized by hepatic steatosis. Despite the growing burden of NAFLD, approved pharmacological treatment is lacking. As an inhibitor of androgen receptor (AR), EPI-001 is being explored for the treatment of prostate cancer. This study aimed to investigate the potential of EPI-001 for treating NAFLD in free fatty acids (FFAs)-induced human hepatic cells and high-fat-high-sugar (HFHS)-feeding mice. Our results showed that EPI-001 reduced lipid accumulation in hepatic cells and ameliorated hepatic steatosis in mouse livers. Further exploration suggested that the effect of EPI-001 was associated with CYP2E1-mediated reduction of reactive oxygen species (ROS). This provides encouraging evidence for further studies on EPI-001 therapy for NAFLD.
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spelling pubmed-97858682022-12-24 Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1 Wang, Shuqin Li, Xue Xu, Weizhe Gao, Jing Wang, Yin Jia, Xiaoyuan Li, Gongchu Pan, Qiuwei Chen, Kan Int J Mol Sci Article Nonalcoholic fatty liver disease (NAFLD) is recognized as a metabolic disease characterized by hepatic steatosis. Despite the growing burden of NAFLD, approved pharmacological treatment is lacking. As an inhibitor of androgen receptor (AR), EPI-001 is being explored for the treatment of prostate cancer. This study aimed to investigate the potential of EPI-001 for treating NAFLD in free fatty acids (FFAs)-induced human hepatic cells and high-fat-high-sugar (HFHS)-feeding mice. Our results showed that EPI-001 reduced lipid accumulation in hepatic cells and ameliorated hepatic steatosis in mouse livers. Further exploration suggested that the effect of EPI-001 was associated with CYP2E1-mediated reduction of reactive oxygen species (ROS). This provides encouraging evidence for further studies on EPI-001 therapy for NAFLD. MDPI 2022-12-16 /pmc/articles/PMC9785868/ /pubmed/36555703 http://dx.doi.org/10.3390/ijms232416063 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Shuqin
Li, Xue
Xu, Weizhe
Gao, Jing
Wang, Yin
Jia, Xiaoyuan
Li, Gongchu
Pan, Qiuwei
Chen, Kan
Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1
title Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1
title_full Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1
title_fullStr Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1
title_full_unstemmed Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1
title_short Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1
title_sort amelioration of hepatic steatosis by the androgen receptor inhibitor epi-001 in mice and human hepatic cells is associated with the inhibition of cyp2e1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785868/
https://www.ncbi.nlm.nih.gov/pubmed/36555703
http://dx.doi.org/10.3390/ijms232416063
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