Schisantherin A interacts with gut bacteria to stimulate adipose tissue thermogenesis in obese mice via a TGR5‒p-CREB‒STAT6 signaling pathway

作者：Xunjiang Wang, Xu Wang, Shenglan Yu, Luyao Huang, Qiongwen Xue, Xinru Yang, Zixuan Wang, Wenyuan Lin, Yaping Jiang, Ying Xu, Qi Liao, Lihua Jin, Zhengtao Wang, Feng Tao, Li Yang, Wendong Huang, Lili Ding · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-67172-y · 被引用次数：3 · 研究领域：Immune cells in cancer、Gut microbiota and health、Plant-derived Lignans Synthesis and Bioactivity

The global epidemic of obesity challenges the scientific and medical communities to find different treatments. Schisantherin A (Sin A), a natural compound isolated from Schisandra chinensis (Turcz.), reduces the abundance of bile salt hydrolase-producing gut bacteria in obese mice, leading to accumulation of specific conjugated bile acids (CBAs). These elevated CBAs activate a signaling axis containing Takeda G protein-coupled receptor 5, phosphorylated cAMP-responsive element binding protein 1, and signal transducer and activator of transcription 6 (TGR5–p-CREB–STAT6), wherein CREB directly binds to the STAT6 promoter. Sin A-induced STAT6 activation promoted M2-like macrophages polarization to secret slit guidance ligand 3 (SLIT3), which consequently stimulated norepinephrine release in sympathetic neurons and induced thermogenesis in adipose tissue. This study thus identifies a pathway by which Sin A interacts with gut bacteria to stimulate CBA-mediated beiging of white adipose tissue, highlighting a promising natural product-based strategy for obesity treatment. Schisantherin A (Sin A), a bioactive lignan from Schisandra chinensis, alleviates obesity and liver fat accumulation in mice, but the mechanisms are incompletely understood. Here the authors show that Sin A mitigates obesity and related metabolic disorders by elevating circulating conjugated bile acids, which in turn modulate adipose tissue thermogenesis in mice.