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 under-lying mechanisms.
Material and Methods: A stable MafF-overexpressing cell line was estab-lished using lentiviral infection. RT-qPCR and Western blot analysis con-firmed MafF expression. Free fatty acid (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 the 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 hepato-cyte steatosis but had little effect on FFA-induced hepatocyte steatosis. MafF overexpression significantly reduced the expression of peroxisome proliferator-activated receptor gamma (PPARG), acetyl-CoA carboxylase (ACC), and lipoprotein lipase (LPL) in hepatocytes. Upon FFA induc-tion, control (NC) cells exhibited downregulation of these genes, whereas MafF-overexpressing cells upregulated LPL expression. In contrast, under ETOH treatment, NC cells upregulated these genes, while MafF-overex-pressing cells showed downregulation.
Conclusion: This study highlighted the regulation of lipid-related genes by MafF, including PPARG, ACC, and LPL, and its effect on FFA- and ETOH-induced hepatocellular lipid accumulation in distinct ways. MafF showed a more pronounced improvement in ETOH-induced hepatocyte ste-atosis, providing crucial insights into MafF’s role in hepatic lipid metabo-lism and potential therapeutic strategies for NAFLD and AFLD.