过表达丝裂原诱导基因6通过抑制内质网应激减少棕榈酸诱导的肝细胞脂质蓄积OA北大核心CSTPCD

AIM:To investigate the effects of mitogen-inducible gene 6(MIG6)overexpression on palmitic acid(PA)-induced endoplasmic reticulum stress-associated steatosis in hepatocytes.METHODS:A mouse model of non-alcoholic steatohepatitis was established by feeding twenty C57BL/6J mice a high-fat diet for 26 weeks.The mice were ran-domly divided into two groups:normal diet control group and high-fat diet group,and their livers were retained for subse-quent experiments.The PA was used to induce lipid accumulation in HepG2 cells and AML12 cells,and the cells were di-vided into two groups:BSA(10%BSA)group and PA(500 µmol/L PA)group.The MIG6 overexpression was induced by transfecting HepG2 and AML12 cells with human and mouse MIG6 overexpression plasmids,respectively.The cells were divided into four groups according to their different treatment conditions:(1)negatiive+BSA group(transfected with nega-tive control plasmid+10%BSA);(2)MIG6+BSA group(transfected with MIG6 overexpression plasmid+10%BSA);(3)negative+PA group(transfected with negative control plasmid+500 µmol/L PA);(4)MIG6+PA group(transfected with MIG6 overexpression plasmid+500 µmol/L PA).Lipid accumulation in hepatocytes was assessed by oil red O staining,and RT-qPCR was used to detect the mRNA expression level of MIG6 in liver tissues.The protein levels of MIG6,lipid synthesis-related molecules fatty acid synthase(FASN)and sterol regulatory element-binding protein 1(SREBP1),and endoplasmic reticulum stress-related proteins glucose regulated protein 78(GRP78)and C/EBP homologous protein(CHOP)in hepatocytes were detected using Western blot.RESULTS:High-fat diet increased the triglyceride content in the liver tissue of C57BL/6J mice induced lipid accumulation in hepatocytes and suppressed the mRNA expression level of MIG6(P<0.01).PA intervention increased the protein levels of lipid synthesis-related molecules such as FASN and SREBP1,and endoplasmic reticulum stress markers GRP78 and CHOP in hepatocytes,but inhibited MIG6 protein levels(P<0.01).We transfected hepatocytes with MIG6 overexpression plasmid,which significantly increased MIG6 protein levels,decreased GRP78 and CHOP protein levels in hepatocytes(P<0.01),significantly attenuated PA-induced lipid accumulation in hepatocytes,and down-regulated FASN and SREBP1 protein levels(P<0.01).These results indicate that MIG6 overexpression inhibited PA-induced endoplasmic reticulum stress and attenuated lipid accumulation in hepato-cytes.CONCLUSION:Overexpression of MIG6 inhibits lipid accumulation in hepatocytes by suppressing endoplasmic reticulum stress.