@article{ZHANG2026, 
author = {Leiying ZHANG and Liyang ZOU and Lingling ZHOU and Xin MA and Xiaomin LIU and Huan YAO and Yuan ZHUANG and Yang YU},
title = {CEBPA promotes hepatic steatosis in metabolic dysfunction-associated fatty liver disease in mice via the SREBP-1c/FASN/ACC axis},
year = {2026},
journal = {Journal of Southern Medical University},
volume = {46},
number = {10},
pages = {2415-2423},
keywords = {metabolic dysfunction-associated fatty liver disease, CCAAT/enhancer-binding protein alpha, sterol regulatory element-binding protein 1c, fatty acid synthesis, lipid metabolism},
url = {https://www.sciopen.com/article/10.12122/j.issn.1673-4254.2026.10.11},
doi = {10.12122/j.issn.1673-4254.2026.10.11},
abstract = {MethodsTo 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).MethodsEight-week-old male C57BL/6J mice were assigned to a control group fed a standard diet or a MAFLD model with high-fat diet (HFD) feeding. Hepatic lipid accumulation and the expression of key molecules in the CEBPA/SREBP-1c pathway were assessed using serum biochemical analysis, Western blotting, and Oil Red O staining. In HepG2 cells, CEBPA and SREBP-1c expression was manipulated by plasmid-mediated overexpression or RNA interference. A sodium palmitate/sodium oleate-induced lipid-overload model was used to mimic lipid overload in vitro. 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.ResultsHFD-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.ConclusionCEBPA 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.}
}