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

ABSTRACT 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 × 10 3 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.