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

Abstract

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.

• Authors: Shuqin Wang, Xue Li, Weizhe Xu, Jing Gao, Yin Wang, Xiaoyuan Jia, Gongchu Li, Qiuwei Pan, Kan Chen
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 24 (Dec 16 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36555703 (Publication Type: Journal Article)

Chemical References

• Cytochrome P-450 CYP2E1
• EPI 001
• Receptors, Androgen

Topics

• Male
• Humans
• Mice
• Animals
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism)
• Cytochrome P-450 CYP2E1 (metabolism)
• Receptors, Androgen (metabolism)
• Liver (metabolism)
• Hepatocytes (metabolism)
• Lipid Metabolism
• Mice, Inbred C57BL
• Diet, High-Fat (adverse effects)