Objective        To determine the effect of SREBP cleavage-activating protein/sterol regulatory element binding protein-1c (SCAP/SREBP-1c) on the lipid synthesis metabolism in hepatocytes under endoplasmic reticulum stress (ERS).      Methods      An endoplasmic reticulum stress model of human L02 hepatocytes was induced by thapsigargin (Tg). Western blotting was used to determine the expression of GRP78. Lipid deposition was detected by triglyceride kit and Oil Red O staining. Real-time quantitative PCR was used to test the expression of ACC1 and FAS at mRNA level

and Western blotting was also applied to measure the protein levels of nSREBP-1c

FAS and ACC1.      Results       Western blot analysis showed that GRP78 protein in the experimental group was remarkably higher than that in the control group (P0.05)

indicating the successful establishment of the ERS model. In Tg group

triglyceride content and lipid droplet were apparently increased (P0.05)

and the nSREBP-1c protein expression was up-regulated (P0.05) and the mRNA and protein levels of FAS and ACC1 were also increased

consistent with the trend of nSREBP-1c protein (P0.05). In SCAP interference group

the above indicators were significantly down-regulated (P0.05).      Conclusion      ERS regulates lipid synthesis metabolism in L02 hepatocytes through SCAP/SREBP-1c

and promotes lipid deposition

which may be important in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Silencing the gene expression of SCAP can reduce the degree of fatty degeneration which was induced by ERS

and can be a safe and effective new target for prevention and treatment of NAFLD.