Cai Jinhui, Wang Shen, Feng Yanmin, Zheng Lin, Liang Qiuting, Liang Yanqing, Ye Xiaoxia
School of Pharmacy, Guangdong Medical University, Zhanjiang, PR China.
Pathological Diagnosis and Research Center, Hospital of Guangdong Medical University, Zhanjiang, PR China.
Hepatol Forum. 2025 Apr 30;6(3):91-98. doi: 10.14744/hf.2024.2024.0030. eCollection 2025.
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.
A stable MafF-overexpressing cell line was established using lentiviral infection. RT-qPCR and Western blot analysis confirmed 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.
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 significantly reduced 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 downregulation of these genes, whereas MafF-overexpressing cells upregulated LPL expression. In contrast, under ETOH treatment, NC cells upregulated these genes, while MafF-overexpressing cells showed downregulation.
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 steatosis, providing crucial insights into MafF's role in hepatic lipid metabolism and potential therapeutic strategies for NAFLD and AFLD.
转录因子MafF是脂肪生成的一种新型调节因子，但其在肝脂肪变性中的作用尚不清楚。本研究旨在探讨MafF对肝细胞脂肪变性的影响及其潜在机制。
利用慢病毒感染建立稳定的MafF过表达细胞系。RT-qPCR和蛋白质免疫印迹分析证实了MafF的表达。使用游离脂肪酸（FFA）或乙醇（ETOH）诱导来模拟非酒精性或酒精性脂肪性肝病（NAFLD或AFLD）中的肝细胞脂肪变性。通过CCK-8检测、钙黄绿素-AM/PI染色和油红O染色评估细胞活性和脂质积累。使用RT-qPCR检测FFA或ETOH处理前后脂质代谢相关基因表达的变化。
FFA或ETOH诱导肝细胞脂质积累，MafF过表达显著改善ETOH诱导的肝细胞脂肪变性，但对FFA诱导的肝细胞脂肪变性影响不大。MafF过表达显著降低肝细胞中过氧化物酶体增殖物激活受体γ（PPARG）、乙酰辅酶A羧化酶（ACC）和脂蛋白脂肪酶（LPL）的表达。在FFA诱导下，对照（NC）细胞这些基因表达下调，而MafF过表达细胞上调LPL表达。相反，在ETOH处理下，NC细胞上调这些基因，而MafF过表达细胞则下调。
本研究强调了MafF对脂质相关基因（包括PPARG、ACC和LPL）的调节作用，以及其以不同方式对FFA和ETOH诱导的肝细胞脂质积累的影响。MafF对ETOH诱导的肝细胞脂肪变性有更显著的改善作用，为MafF在肝脏脂质代谢中的作用以及NAFLD和AFLD的潜在治疗策略提供了重要见解。
