Preparation of protein and its preventive effect on nonalcoholic fatty liver disease in mice.

is a valuable edible fungus with multidimensional bioactivities; however, research on protein and its beneficial effects on nonalcoholic fatty liver disease (NAFLD) have been limited. In this study, protein (MEP) with 80.59% protein content was prepared, isolated, and characterized by the complete amino acid composition. The main molecular weight of the protein ranged from 65 to 120 kDa, with 100 kDa being the most dominant band, and it exhibited an alpha helix structure when analyzed by FT-IR and circular dichroism analysis. MEP could regulate body weight, fat accumulation, and alleviate lipid metabolism in adipose tissues in mice with high-fat diet-induced NAFLD. MEP prevented hepatic lipotoxicity, which was reflected in attenuating liver steatosis and , thereby regulating the levels of related factors involved in lipid metabolism (, PPARs, HNF-4, SREBP, FASN, ACC-1, and CD36). Furthermore, it inhibited oxidative stress response, which can be attributed to the activation of the MAPK/PGC-1α pathway. Additionally, MEP exhibited probiotic effects, as demonstrated by the altered gut microbiota composition and improved the intestinal barrier integrity. Thus, this study confirmed the preventive effect of MEP against NAFLD by regulating the gut-liver cross-talk, which provided a theoretical basis for the development and utilization of .