Effect of Hesperidin Supplementation on Liver Metabolomics and Gut Microbiota in a High-Fat Diet-Induced NAFLD Mice Model

The present study investigated the mechanism underlying the impact of hesperidin (HES) on nonalcoholic fatty liver (NAFLD). C57BL/6J male mice were administered a low-fat diet, high-fat diet (HFD), or HFD plus 0.2% (wt/wt) HES (HFD + HES) diet. After 16 weeks of intervention, the mice in the HFD+HES group showed a lower final body weight and liver weight and improved serum lipid profiles when compared with the HFD group. Alleviation of liver dysfunction induced by HFD was observed in HES-fed mice, and the expression of genes involved in lipid metabolism was also altered. Moreover, HES changed the composition of the intestinal microbiota and enriched specific genera such as Bacteroidota. Liver metabolomics analysis indicated that HES enhanced the abundance of metabolites in arginine-related as well as mitochondrial oxidation-related pathways, and these metabolites were predicted to be positively correlated with the gut genera enriched by HES. Together, these results indicate that HFD-fed mice supplemented with HES showed a markedly regulated hepatic metabolism concurrent with shifts in specific gut bacteria.