Work

[CEBPA promotes hepatic steatosis in metabolic dysfunction-associated fatty liver disease in mice via the SREBP-1c/FASN/ACC axis].

Year: 2026

Type: article

Abstract: METHODS: To investigate the role of CCAAT/enhancer-binding protein alpha (CEBPA) in metabolic dysfunction-associated fatty liver disease (MAFLD) and whether CEBPA promotes hepatocellular lipogenesis by regulating sterol regulatory element-binding protein-1c (SREBP-1c). METHODS: . Quantitative PCR, Western blotting, Oil Red O staining, and reciprocal rescue experiments were performed to explore the regulatory relationship between CEBPA and SREBP-1c and their effects on lipogenic markers. RESULTS: HFD-fed mice developed marked hepatic steatosis with increased serum TC, TG, LDL-C, and FFA levels, significantly upregulated hepatic protein expression of CEBPA, SREBP-1c, fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC), and enhanced lipid deposition. In HepG2 cells, SREBP-1c knockdown reduced FASN and ACC expression, whereas SREBP-1c overexpression increased their expression in both basal and lipid-overload conditions. Similarly, CEBPA knockdown suppressed SREBP-1c, FASN, and ACC expression and reduced intracellular lipid accumulation, while CEBPA overexpression produced the opposite effects. Rescue experiments showed that SREBP-1c overexpression partially reversed the inhibitory effects of CEBPA knockdown on FASN and ACC, whereas SREBP-1c silencing attenuated CEBPA-induced upregulation of these lipogenic molecules. CONCLUSIONS: CEBPA promotes hepatic lipogenesis possibly by regulating the SREBP-1c/FASN/ACC axis in both basal and lipid-overload conditions, suggesting that the CEBPA-SREBP-1c pathway contributes to hepatic steatosis in MAFLD and represents a potential therapeutic target.

Source: PubMed Central

DOI: 10.12122/j.issn.1673-4254.2026.10.11