Sanghuangporus vaninii-fermented green tea targets FoxO1/SIRT1 to alleviate obesity via integrated network pharmacology and multi-omics

Building on prior evidence of enhanced in vitro lipid-lowering activity of Sanghuangporus vaninii -fermented green tea, this study evaluated its anti-obesity mechanisms in high-fat diet-induced obese mice. Components of the fermented tea were characterized, and network pharmacology predicted potential lipid-modulating targets. Seventy male C57BL/6 J mice were allocated to seven groups: a normal diet group, a high-fat diet group, a high-fat diet group treated with orlistat (positive control), and high-fat diet groups treated with either non-fermented tea or the fermented tea product at two dosages (200 or 400 mg/kg/day). After a four-week intervention, the fermented tea product significantly reduced body weight, serum total cholesterol, and hepatic lipid accumulation compared to the high-fat diet controls. Treatment also enhanced gut microbial diversity, reduced the Firmicutes/Bacteroidetes ratio, and increased fecal triglyceride excretion. Hepatic transcriptomics revealed upregulation of genes including Gadd45a and Bcl6 , with pathway analysis confirming involvement in FoxO signaling. Mechanistically, the fermented tea product suppressed hepatic lipogenic genes while upregulating markers of fatty acid oxidation and lipolysis, consistent with network pharmacology predictions. These findings demonstrate that the fermented tea product alleviates diet-induced obesity through coordinated modulation of hepatic lipid metabolism and gut microbiota, outperforming non-fermented tea and providing novel insights into fermented tea as a dietary intervention. • S. vaninii -fermented tea targets FoxO1/SIRT1 against obesity. • TFS remodels gut microbiota, increases fecal lipid excretion. • TFS suppresses lipogenesis and activates hepatic β-oxidation. • Fungal fermentation enhances anti-obesity efficacy of green tea.