Background and Aim: The transcription factor MafF is a novel regulator of adipogenesis, but its role in hepatic steatosis remains unclear. This study aimed to explore the impact of MafF on hepatocyte steatosis and its underlying mechanisms.
Material and Methods: A stable MafF-overexpressing cell line was established using lentiviral infection. RT-qPCR and Western blot analysis confirmed MafF expression. Free fatty acids (FFA) or ethanol (ETOH) induction was used to simulate hepatocyte steatosis in non-alcoholic or alcoholic fatty liver disease (NAFLD or AFLD). Cell activity and lipid accumulation were assessed through CCK-8 assay, Calcein-AM/PI staining, and oil red O staining. The changes in lipid metabolism-related gene expression before and after FFA or ETOH treatment were detected using RT-qPCR.
Results: FFA or ETOH-induced lipid accumulation in hepatocytes, and overexpression of MafF significantly ameliorated ETOH-induced hepatocyte steatosis, but had little effect on FFA-induced hepatocyte steatosis. MafF overexpression could significantly reduce the expression of peroxisome proliferator-activated receptor Gamma (PPARG), acetyl-CoA carboxylase (ACC), and lipoprotein lipase (LPL) in hepatocytes. Upon FFA induction, control（NC） cells exhibited down-regulation of these genes, whereas MafF-overexpressing cells up-regulated LPL expression. In contrast, under ETOH treatment, NC cells up-regulated these genes, while MafF-overexpressing cells showed a down-regulation.
Conclusion: This study highlighted the regulation of lipid-related genes by MafF, including PPARG, ACC, and LPL, and affected FFA and ETOH-induced hepatocellular lipid accumulation in distinct ways, and MafF showed a more pronounced improvement in ETOH-induced hepatocyte steatosis, providing crucial insights into MafF’s role in hepatic lipid metabolism and potential therapeutic strategies for NAFLD and AFLD.