Hepatoprotective effects of polysaccharide from Morchella esculenta are associated with activation of the AMPK/Sirt1 signaling pathway in mice with NAFLD

The functional food application of edible fungus polysaccharides has been widely studied based on their variety of potential pharmacological activities. However, the hepatoprotective effects and mechanisms of Morchella esculenta polysaccharide against nonalcoholic fatty liver disease (NAFLD) remain unknown. A high-fat diet (HFD) fed C57BL/6 J mice for 8 weeks was employed to establish NAFLD with simple steatosis, methionine choline deficiency (MCD) diet for 4 weeks induced hepatic steatohepatitis and fibrosis. The M. esculenta polysaccharide (MCP) or saline was administered intragastrically. MCP markedly reduced hepatic and serum triglyceride (TG) and cholesterol contents in HFD-fed mice. Moreover, treatment with MCP ameliorated nonalcoholic steatohepatitis (NASH) progression in MCD-fed mice, as evidenced by ameliorated hepatic steatosis, inflammatory response, and fibrosis. Mechanistically, MCP suppressed the expression of lipogenic genes and inflammatory cytokines and upregulated peroxisome proliferator-activated receptor (PPAR)-alpha expression to induce fatty acid R-oxidation. These beneficial effects were attributed to activating the AMP-activated kinase (AMPK)/Sirtuin 1 (Sirt1) signaling pathway. Therefore, we provided evidence that MCP might be an effective dietary supplement to ameliorate NAFLD.