Highly expressed MT-ND3 positively associated with histological severity of hepatic steatosis

Hepatic steatosis is the accumulation of an excess amount of triglycerides and other fats inside liver cells resulting from abnormal hepatic lipid metabolism. Mitochondrial structural and molecular defects are involved in the progression of hepatic steatosis pathogenesis. Hepatic methylation and transcriptional activity of the mitochondrial-encoded NADH dehydrogenase (MT-ND) play a critical role in the progression of non-alcoholic fatty liver disease (NAFLD). However, the expression of MT-ND3 in hepatic steatosis has not been extensively studied. In this study, liver specimens were collected from different patients, and were subjected to immunohistochemistry. Primary hepatocytes were treated with oxidative stress, hypoxia, and lipotoxicity to investigate the respective roles of these factors on MT-ND3 expression and cell apoptosis by western blotting and flow cytometry, respectively. We found that increased MT-ND3 expression in human hepatic steatosis was positively associated with histological severity of hepatic steatosis. Hypoxia, H2O2 , and saturated fatty acid treatment induced cell apoptosis mediated by mitochondria. These three factors all had effects on MT-ND3 expression in cultured hepatocytes. Taken together, MT-ND3 may play important roles in hepatic steatosis progress. Hypoxia, oxidative stress, and lipotoxicity could all influence expression of MT-ND3 and thus may play a role in the progression of hepatic steatosis.