Amelioration of Hepatic Steatosis by the Androgen Receptor Inhibitor EPI-001 in Mice and Human Hepatic Cells Is Associated with the Inhibition of CYP2E1.
Shuqin WangXue LiWeizhe XuJing GaoYin WangXiaoyuan JiaGongchu LiMaikel P PeppelenboschKan ChenPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- induced apoptosis
- prostate cancer
- cell cycle arrest
- reactive oxygen species
- endothelial cells
- cell death
- fatty acid
- endoplasmic reticulum stress
- oxidative stress
- dna damage
- high fat diet induced
- high glucose
- adipose tissue
- cell proliferation
- metabolic syndrome
- climate change
- skeletal muscle
- insulin resistance
- pi k akt
- replacement therapy
- drug administration