Polysaccharides from Lactarius volemus Fr. ameliorate high-fat and high-fructose diet induced metabolic disorders and intestinal barrier dysfunction.

Our research was conducted to investigate the effects of Lactarius volemus Fr. polysaccharides (LVP) on metabolic disorders and intestinal barrier dysfunction in HFFD-induced obese mice. Our findings demonstrated that LVP supplementation significantly ameliorated hyperlipoidemia and hyperglycemia, insulin resistance and hepatic inflammation. Additionally, LVP alleviated hepatic steatosis and histological lesions, as well as hepatic function dysbiosis. The underlying mechanism may involve the regulation of hepatic insulin signaling transduction pathway such as IRS1/AKT pathway and the suppression of MAPKs signaling pathway. Furthermore, LVP intervention improved intestinal barrier function and reduced intestinal permeability by enhancing the expression of tight junction proteins and restoring intestinal microbiota composition. In summary, our results provided evidence that LVP exerted beneficial effects on HFFD-induced metabolic disorders along with restoration of intestinal barrier function and reduction in endotoxin levels. These outcomes are associated with maintenance of gut microbiota homeostasis and up-regulation of Short-Chain Fatty Acids (SCFAs). Furthermore, butyric acid was found to restrict lipid accumulation in OA-induced HepG2 hepatocytes while strengthening intestinal barrier integrity in LPS-induced Caco-2 cells. Thus, polysaccharides LVP may serve as a potential prebiotic or health supplement in the prevention and treatment of obesity-related metabolic disorders.