Alleviation Effects of Microbial Metabolites from Resveratrol on Non-Alcoholic Fatty Liver Disease

Resveratrol (RSV), a polyphenolic stilbene, has been widely studied for its protective effects against non-alcoholic fatty liver disease (NAFLD) by modulating intestinal microbiota. The microbial metabolites after RSV supplement would contribute to the bioeffects of RSV, while their impacts on NAFLD were unclear. Therefore, this study aimed to investigate the beneficial effects of the main microbial metabolites from RSV on lipid metabolism by combining in vitro and in vivo models. The mice were fed a high-fat diet and injected with RSV, 3-hydroxyphenyl propionic acid (3-HPP), and 4-HPP for 13 weeks (n = 6). Body weight, serum parameters, histological analysis, and gene expression involved in lipid metabolism were quantified. Our results suggested that 100 μM of 3-HPP and 4-HPP inhibited lipid accumulation more significantly than parent RSV in an oleic acid-induced HepG2 cell line. Furthermore, 3-HPP, 4-HPP, and RSV effectively reduced liver weight and body weight, improved hepatic steatosis, and alleviated systemic inflammation in NAFLD mice. In addition, the results of quantitative real-time PCR showed that 3-HPP and 4-HPP altered the expression of cholesterol influx and efflux genes to a stronger extent than RSV. These results indicate that 3-HPP and 4-HPP are effective in regulating hepatic lipid metabolism.