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<p>The global epidemic of obesity challenges the scientific and medical communities to find different treatments. Schisantherin A (Sin A), a natural compound isolated from <i>Schisandra chinensis</i> (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 <i>STAT6</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月11日

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  • 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

摘要

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.