Fenofibrate improves hepatic steatosis, insulin resistance, and shapes the gut microbiome via TFEB-autophagy in NAFLD mice.

Non-alcoholic fatty liver disease (NAFLD) is a major liver disease subtype worldwide, is commonly associated with insulin resistance and obesity. NAFLD is characterized by an excessive hepatic lipid accumulation, as well as hepatic steatosis. Fenofibrate is a peroxisome proliferator-activated receptor α agonist widely used in clinical therapy to effectively ameliorate the development of NAFLD, but its mechanism of action is incompletely understood. Here, we found that fenofibrate dramatically modulate the gut microbiota composition of high-fat diet (HFD)-induced NAFLD mouse model, and the change of gut microbiota composition is dependent on TFEB-autophagy axis. Furthermore, we also found that fenofibrate improved hepatic steatosis, and increased the activation of TFEB, which severed as a regulator of autophagy, thus, the protective effects of fenofibrate against NAFLD are depended on TFEB-autophagy axis. Our study demonstrates the host gene may influence the gut microbiota and highlights the role of TFEB and autophagy in the protective effect of NAFLD. This work expands our understanding of the regulatory interactions between the host and gut microbiota and provides novel strategies for alleviating obesity.

Fagopyrum dibotrys extract alleviates hepatic steatosis and insulin resistance, and alters autophagy and gut microbiota diversity in mouse models of high-fat diet-induced non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a major global health concern with increasing prevalence, with a lack of currently available effective treatment options; thus, the investigation of novel therapeutic approaches is necessary. The study aimed to investigate the outcomes and mechanisms of action of Fagopyrum dibotrys extract (FDE) in a high-fat diet (HFD)-induced mouse model of obesity. The findings showed that FDE supplementation attenuated glucose tolerance, insulin resistance (IR), hepatic steatosis, and abnormal lipid metabolism. In addition, FDE also promoted autophagic activity and inhibited the phosphorylation of transcription factor EB in HFD-fed mice. Furthermore, gut microbiota characterization via 16S rRNA sequencing revealed that the supplementation of FDE increased Bacteroidetes and Verrucomicrobia populations while decreased Firmicutes, thus modifying the gut microbiome. FDE also increased the relative abundance of Akkermansia. Our findings suggest that FDE may protect against HFD-induced NAFLD by activating autophagy and alleviating dysbiosis in the gut microbiome. FDE may be beneficial as a nutraceutical treatment for NAFLD.