CYP1A2 contributes to alcohol-induced abnormal lipid metabolism through the PTEN/AKT/SREBP-1c pathway

Abstract

Abnormal liver lipid metabolism results in a series of liver diseases and contributes to tumourigenesis. The expression and activity of Cytochrome P450 1A2 (CYP1A2) is significantly increased in alcoholic fatty liver according to our previous studies. In this study, we aimed to explore the role of CYP1A2 in lipid metabolism abnormalities induced by alcohol and to investigate the underlying mechanisms. L02 cells were treated with siRNA-CYP1A2 or fluvoxamine and then stimulated with 100 mM ethanol for 24 h. The levels of ALT and TGs in the siRNA-CYP1A2 and fluvoxamine groups were significantly lower than those in the normal control group after ethanol treatment, and the expression of SREBP-1c was decreased when CYP1A2 was inhibited, suggesting that CYP1A2 may contribute to alcohol-induced irregular lipid metabolism by regulating sterol regulatory element-binding protein-1c (SREBP-1c). The expression of phosphatase and tensin homologue deleted on chromosome ten (PTEN) was decreased in normal cells, and it was further reduced when the expression of CYP1A2 was downregulated. Overexpression of PTEN led to decreased expression of p-AKT and SREBP-1c, which were elevated in both the normal and transfected groups after ethanol stimulation. In contrast, when PTEN was inhibited by siRNA-PTEN or bpv, the expression of PTEN was reduced in each group after ethanol treatment, while the expression of p-AKT and SREBP-1c was increased significantly. These results demonstrate that CYP1A2 may participate in the abnormal lipid metabolism caused by alcohol stimulation through the PTEN/AKT/SREBP-1c pathway.