Ferulic acid ameliorates nonalcoholic fatty liver disease and modulates the gut microbiota composition in high-fat diet fed ApoE−/− mice

The objective of this study was to investigate the effects of ferulic acid (FA) on nonalcoholic fatty liver disease (NAFLD) and gut microbiota, and its regulation mechanism in ApoE−/− mice fed on a high-fat diet (HFD). Liver morphology, blood lipids, gut microbiota and their metabolite indole-3-acetic acid (I3A) were determined in ApoE-/- mice. We also examined the hepatic expression of aryl hydrocarbon receptor (AHR), which inhibits the expression of fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c), and ultimately reduces the deposition of triglycerides (TG) and total cholesterol (TC) in the liver. The results of the animal experiment showed that oral administration of FA markedly alleviated the formation of NAFLD and decreased the levels of serum TC, TG and low-density lipoprotein cholesterol (LDL-C). Furthermore, FA supplementation altered the composition of gut microbiota, in particular, modulating the ratio of Firmicutes to Bacteroidetes, and decreased the generation of I3A. Additionally, FA could increase the expression of hepatic AHR and inhibit the expression of FASN and SREBP-1c in the liver. Finally, we found that FA did not have hepatorenal toxicity. The findings above illustrate that FA has the potential to ameliorate NAFLD, some of which are closely related to the modulation of specific gut microbiota and the regulation of genes involved in TG and TC metabolism.