A Novel Polysaccharide From Tremella fuciformis Alleviated High-Fat Diet-Induced Obesity by Promoting AMPK/PINK1/PRKN-Mediated Mitophagy in Mice

Scope: Polysaccharides from Tremella fuciformis have gained significant interest due to their diverse biological activities. This study focuses on characterizing a purified polysaccharide, TPSP2, extracted from T. fuciformis and evaluating its antiobesity effect and underlying mechanisms in vivo. Methods and results: Structural analysis revealed that TPSP2, with a molecular weight of 1.51 x 103 kDa, is composed of mannose, rhamnose, glucuronic acid, galactose, xylose, arabinose, and fucose in specific molar ratios. The primary linkages identified include t-Fuc(p), 1,2-Xyl(p), t-GlcA(p), 1,3-Man(p), and 1,2,3-Man(p), with their corresponding ratios being 12.987%, 11.404%, 16.050%, 16.527%, and 26.624%, respectively. In vivo experiments demonstrated that TPSP2 significantly alleviated high-fat diet-induced weight gain, hyperlipidemia, hepatic steatosis, hyperglycemia, and insulin resistance in mice. Mechanistically, TPSP2 was found to enhance AMPK/PINK1-PRKN-dependent mitophagy by upregulating the p-AMPK/AMPK ratio, LC3-II/I ratio, and expression of PINK1, PRKN, prohibitin 2 (PHB2), and LAMP2, while downregulating p62 and TOM20 expression. Conclusion: This study suggested that TPSP2 could be a promising candidate for addressing obesity-related metabolic disorders by targeting mitochondrial quality control mechanisms.