Protective Effects of Hydroxyphenyl Propionic Acids on Lipid Metabolism and Gut Microbiota in Mice Fed a High-Fat Diet

Gut microbiota imbalances lead to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is primarily accompanied by hepatic steatosis. Hydroxyphenyl propionic acids (HPP) have shown great potential in inhibiting lipid accumulation but their protective effects concerning NAFLD and intestinal microbiota have remained unclear. In this paper, we investigated the efficacies of 3-HPP and 4-HPP on hepatic steatosis and gut flora in mice fed a high-fat diet (HFD). We found that 3-HPP and 4-HPP administration decreased body weight and liver index, ameliorated dyslipidemia, and alleviated hepatic steatosis. Furthermore, 3-HPP and 4-HPP enhanced the multiformity of gut microbiota; improved the relative abundance of GCA-900066575, unidentified_Lachnospiraceae, and Lachnospiraceae_UCG-006 at genus level; increased concentration of acetic acid, propionic acid and butanoic acid in faeces; and reduced systemic endotoxin levels in NAFLD mice. Moreover, 4-HPP upregulated the relative abundance of genera Rikenella and downregulated the relative abundance of Faecalibaculum. Furthermore, 3-HPP and 4-HPP regulated lipid metabolism and ameliorated gut dysbiosis in NAFLD mice and 4-HPP was more effective than 3-HPP.