The Role Of NRF2 In The Development Of NAFLD Via Regulation Of Autophagy

Objects:To investigate the role of NRF2 in the development of NAFLD.Methods:Male C57BL/6J mice?WT?and NRF2 knockout mice(Nrf2^-/-)were challenged with normal diet?ND?or high fatty diet?HFD?.Mouse body weight,liver weight,serum fatty acid metabolism index and liver TG level were detected.Liver was stained by HE and Oil Red O.mRNA expression level of NRF2 and protein expression level were detected by RT-PCR and western blotting respectively.Primary hepatocytes were isolated and treated with free fatty acids to detect the expression level of NRF2,LC3 and p62.Results:Firstly,it showed an increased expression of NRF2 in liver tissue of WT mouse treated with HFD.Compared with WT mouse,Nrf2^-/-mice showed higher liver weight,serum TG and cholesterol and severe fatty acid accumulation of liver.Secondly,the primary hepatocytes obtained from WT mouse also exhibited an enhanced expression of NRF2 after FFAs intervention.And the Nrf2^-/-primary hepatocytes gained more fatty acid accumulation in cytoplasm than WT.At last,the expression level of LC3 and p62 were significantly declined in Nrf2^-/-mouse compared with WT mouse in both liver tissue and primary hepatocytes.Conclusion:HFD treatment enhanced the expression of NRF2 while NRF2 knockout significantly aggravates NAFLD.And NRF2 is involved in the fatty acid metabolism and accumulation in liver via regulating the expression of LC3 and p62.