Effect of homocysteine-mediated endoplasmic reticulum stress on lipid metabolism in hepatocytes

AIM: To explore the effect of homocysteine (Hcy)-mediated endoplasmic reticulum stress on lipid metabolism in hepatocytes.METHODS: HepG2 cells used in the study were treated with 5 mmol/L Hcy.The concentrations of Hcy,triglycerides (TGE) and cholesterol (CHO) in the cells were measured.In high methionine diet-induced hyperhomocysteinemia C57BL/6 mice,the concentrations of TGE and CHO in hepatocytes were analyzed.The mRNAs and proteins expressions of glucose-regulated protein 78 (GRP-78) and sterol regulatory element binding protein (SREBP-1) were also assessed.RESULTS: The concentrations of Hcy and lipids (TGE,CHO) in HepG2 cells at different time point were elevated after treated with 5 mmol/L Hcy (P<0.05,vs 0 hour).The levels of plasma Hcy and TGE or CHO in hepatocytes of high methionine diet mice at different time point were significantly increased (P<0.05,vs 0 week).However,the TGE and CHO levels in plasma had no change (P>0.05,vs 0 week).The mRNAs and proteins expressions of GRP-78 and SREBP-1 in mice at different time point after high methionine diet were higher than that at 0 week (P<0.05).CONCLUSION: It suggests that Hcy-induced endoplasmic reticulum stress causes dysregulation of the endogenous sterol response pathway,also increases hepatic biosynthesis and uptake of TGE and CHO.