Folic acid intervention ameliorates hepatic steatosis after long-term alcohol exposure by alleviating endoplasmic reticulum stress.

In this study, the protective effect of folic acid on alcoholic fatty liver (AFL) was investigated. Eighty C57BL/6 J mice were assigned randomly to the saline control group, folic acid control group, ethanol model group, and folic acid + ethanol model group. After 10 weeks of intervention, folic acid intervention markedly decreased the liver index, serum ALT, serum TG, and hepatic TG levels. The HE and transmission electron microscopy revealed that folic acid intervention alleviated histopathological changes of hepatic steatosis. Western blot revealed that folic acid downregulated the protein levels of GRP78, p-PERK, p-eIF2α, p-IRE1α, XBP1, ATF6, SREBP-1c, FAS, and ACC. In conclusion, our findings demonstrated that folic acid intervention may relieve ethanol-induced ERs by inhibiting PERK-eIF2α, IRE1α-XBP1, and ATF6 signaling pathways, suggesting that folic acid may be a feasible preventive strategy for AFL.