Protective effects of docosahexaenoic acid against non-alcoholic hepatic steatosis through activating of JAK2/STAT3 signaling pathway

Non-alcoholic fatty liver disease is the most common cause of hepatic dysfunction. In the present study, human normal hepatocyte L02 cells were treated with 50% fetal bovine serum to induce the formation of hepatic steatosis in vitro, and then the cells were treated with docosahexaenoic acid to investigate its protective effect on Non-alcoholic fatty liver disease. Our results showed that 50% of fetal bovine serum significantly induced intracellular lipid accumulation and hepatocyte fatty degeneration within 48 h. The expression level of adipose formation-related genes was significantly up-regulated, such as PPARγ, C/EBPα and SREBP-1; meanwhile, the content of cellular total lipid, total cholesterol and triglycerides were significantly increased after 50% fetal bovine serum treatment. Interestingly, docosahexaenoic acid treatment could inhibit FBS-induced intracellular lipid accumulation in L02 cells and the expression of lipogenic genes. Moreover, docosahexaenoic acid treatment could reduce hepatic steatosis-induced oxidative stress and endoplasmic reticulum stress response, and these responses were shown by the modification of antioxidant enzyme activities and GRP78, CHOP expression. In addition, the results showed that docosahexaenoic acid can activate the JAK2/STAT3 signaling pathway in fatty liver L02 cell; inhibition of JAK2/STAT3 signaling pathway by WP1066 abolished the beneficial effects of docosahexaenoic acid on hepatic steatosis accompanied with the increased expression of lipogenic genes and endoplasmic reticulum stress response. Above all, the present study showed that docosahexaenoic acid can alleviate non-alcoholic hepatic steatosis by activating JAK2/STAT3 signaling pathway.