Structural Characterization of Polysaccharide from Flammulina velutipes and Its Impact on Hyperlipidemia Through Modulation of Hepatic Cholesterol Metabolism and Gut Microbiota

FVPB1, a novel heteropolysaccharide, was extracted from the <i>Flammulina velutipes</i> fruiting body, and its structure was determined by methylation analysis, nuclear magnetic resonance (NMR) spectroscopy. FVPB1 demonstrated efficacy in inhibiting lipid accumulation in Raw264.7 cells and zebrafish, as well as in reducing weight gain and ameliorating liver injury in high-fat diet-induced mice. High concentration of FVPB1 significantly increased serum ApoA1 levels, while all tested doses (low, medium, and high) reduced serum ApoB levels in mice. Intervention with FVPB1 significantly increased the mRNA expression of Lcat and Cyp7a1 enzymes while markedly reducing the transcriptional level of Hmgcr reductase. Additionally, low concentration of FVPB1 enhanced CYP7A1 protein expression, whereas medium and high concentrations of FVPB1 promoted LCAT protein expression. Medium and high concentrations of FVPB1 significantly enhanced bile acid excretion in mice, with the high dose additionally promoting fecal sterol output. Alpha and beta diversity analyses demonstrated that a high-fat diet induced substantial dysbiosis in the gut microbiota of mice, characterized by reduced microbial diversity and richness. Intervention with FVPB1 significantly modulated the structural composition of the intestinal microbiota in high-fat diet-fed mice. Therefore, FVPB1 exerts lipid-lowering effect in high-fat diet-fed mice by modulating cholesterol metabolism and ameliorating gut microbiota dysbiosis.