Fgf21-Dubosiella axis mediates the protective effects of exercise against NAFLD development

AIMTo explore the mechanism of gut microbiota mediates protective effects of exercise against non-alcoholic fatty liver disease (NAFLD) development.MAIN METHODSThe male C57BL/6 mice were fed with high fat food (HFD) or normal diet (CON) respectively, and the obese mice were randomly divided into sedentariness (HFD) and exercise groups (HFD + Exe). The total intervention period was 18 weeks. Antibiotic treatment and fecal microbiota transplantation were applied to evaluate gut microbiota mediates the protective effects of exercise against NAFLD development. 16S rDNA profiling of gut microbiota and extracorporeal rehydration of Dubosiella newyorkensis were performed to identify the crucial role of Dubosiella in NAFLD improvement during exercise training. FGF21 knock-out mice were used to reveal the potential mechanism of exercise increased the abundance of Dubosiella. RT-PCR, Western blot, Histopathological examinations and Biochemical testing were performed to evaluate the lipid deposition and function in the liver.KEY FINDINGSTreadmill exercise significantly ameliorated hepatic function and mitigated lipid accumulation in NAFLD mice, and these hepatoprotective benefits were mostly mediated by the Dubosiella. In addition, the increased abundance of Dubosiella during exercise training was modulated by FGF21 specifically.SIGNIFICANCEIn short, Dubosiella, chiefly regulated by FGF21 signaling during exercise training, has been discovered to govern the protective impacts of exercising counter to the development of NAFLD and exhibits a promising treatment target for NAFLD.