Objective: To investigate the role and mechanism of hepatitis B virus (HBV)-encoded X
protein (HBx) on the regulation of lipid metabolism and proliferation of human
hepatoma cell line HepG2. Methods: HepG2 cells were transiently transfected with HBx expressing plasmid, and the cell proliferation was detected by MTT assay. Lipid droplet accumulation condition was stained by
Oil Red O. Western blot was used to detect the
protein levels of lipid metabolism-related genes, such as
CCAAT/enhancer binding protein α (C/EBPα),
sterol regulatory
element binding protein-1 (SREBP-1),
fatty acid synthetase (FASN) and
acetyl-CoA carboxylase (ACC1). Methyl thiazolyl tetrazolium (MTT),
Oil Red O staining and western blot were used to detect the effect of HBx on the regulation of lipid metabolism and proliferation of HepG2 cells under the conditions of overexpression and low expression of C/EBPα. Results: HBx had significantly promoted the proliferation of
hepatoma cell line HepG2 in dose-and time-dependent manner (F = 32.82, P < 0.001; F = 58.21, P < 0.001). HBx had significantly promoted the
lipid accumulation in HepG2 cells (F = 22.65, P < 0.001). Additionally, the
protein levels of C/EBPα and SREBP-1 (key regulatory factors of lipid metabolism), and the rate-limiting
enzymes FASN and ACC1 were significantly increased. C/EBPα overexpression had further strengthened the effect of HBx on HepG2 cell proliferation, lipid droplet accumulation, and
lipid production-related gene expression. On the contrary, C/EBPα low expression had weakened HBx's promotional effect on cell proliferation, lipid droplet accumulation and
lipid production-related gene expression. Conclusion: HBx may affect the
lipid production and promote the proliferation of human
hepatoma cell line HepG2 via the C/EBPa/SREBP-1 signaling pathway.