Fractionation of Bioactive Polysaccharides from Volvariella volvacea and Their Ameliorative Effects on Hepatic Lipid Accumulation

Volvariella volvacea is a widely consumed edible mushroom, yet the lipid-lowering potential of its polysaccharides remains poorly understood. In this study, two polysaccharide-enriched fractions, VVP-1 and VVP-2, were isolated from V. volvacea fruiting bodies, with weight-average molecular weights of 13,789 and 17,829 Da, respectively. Their lipid-lowering effects were evaluated in palmitic acid (PA)-challenged AML12 mouse hepatocytes and in high-fat diet (HFD)-induced obese male C57BL/6J mice. Both fractions reduced PA-induced intracellular triglyceride (TG) levels in a dose-dependent manner, with VVP-2 showing a trend of greater efficacy. At the molecular level, VVP-2 exposure was associated with downregulation of the lipogenic genes Acaca and Srebf1, upregulation of the fatty acid oxidation-related genes Cpt1a and Ppara, decreased secretion of TNF-α, IL-6, and IL-1β, preservation of mitochondrial signal, restoration of mitochondrial membrane potential, and enhanced ATP production. In HFD-fed mice, VVP-2 (100 mg/kg) attenuated body-weight gain by 38.9%, reduced liver weight by 28.9% and epididymal, inguinal, and perirenal fat weights by 50.3%, 47.5%, and 28.8%, respectively, improved the serum lipid profile (TG reduced by 39.1%, TC by 33.5%, NEFA by 56.2%, and LDL-C by 56.8%), and alleviated hepatic lipid accumulation and liver injury. These findings suggest that VVP-2 may improve mitochondrial function and modulate lipid metabolism-related gene expression, potentially reducing lipid accumulation and inflammation in hepatocytes. These results support the potential of VVP-2 as a lipid-lowering functional food ingredient for the prevention of metabolic dysfunction-associated steatotic liver disease.