Bisphenol S (BPS) is widely used as a substitute for Bisphenol A (BPA). While perinatal BPS exposure is suspected to increase susceptibility to high-caloric diet-induced adipogenesis, how BPS affects offspring remains largely unknown. This study explored effects of prenatal BPS exposure on adiposity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 offspring, revealing significant changes in body weight, glucose tolerance, insulin sensitivity, and histopathology. Employing nontargeted metabolomics and 16S rRNA sequencing, we constructed a comprehensive atlas of metabolome and microbiome shifts across heart, liver, pancreas, white adipose tissue (WAT), brown adipose tissue (BAT), and feces. Male offspring showed greater metabolic and microbial disturbances. Low-dose BPS exposure (0.05 mg/kg/d) induced changes across entire atlas comparable to high-dose (5 mg/kg/d). BAT and WAT were key target tissues with the most significant metabolic disturbances. BPS disrupted fatty acid β-oxidation in WAT by reducing carnitine carriers, causing WAT fat accumulation. A resistance mechanism to BPS exposure was indicated by both mobilization of BAT compensatory thermogenesis, characterized by increased carnitines and UCP1 expression, and an increase in beneficial commensal bacteria. Their competition and imbalance contributed to obesity and insulin resistance in offspring, highlighting the potential for early interventions targeting key metabolites and microbiota.

中文翻译：

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多组织代谢组和微生物组变化的综合图谱：探索高脂肪饮食喂养的后代围产期双酚 S 暴露诱导的肥胖和胰岛素抵抗


双酚 S （BPS） 被广泛用作双酚 A （BPA） 的替代品。虽然怀疑围产期 BPS 暴露会增加对高热量饮食诱导的脂肪生成的易感性，但 BPS 如何影响后代在很大程度上仍然未知。本研究探讨了产前 BPS 暴露对高脂饮食 （HFD） 喂养的 C57BL/6 后代肥胖和胰岛素抵抗的影响，揭示了体重、葡萄糖耐量、胰岛素敏感性和组织病理学的显着变化。采用非靶向代谢组学和 16S rRNA 测序，我们构建了心脏、肝脏、胰腺、白色脂肪组织 （WAT）、棕色脂肪组织 （BAT） 和粪便的代谢组和微生物组变化的综合图谱。雄性后代表现出更大的代谢和微生物干扰。低剂量 BPS 暴露 （0.05 mg/kg/d） 诱导的整个寰谱变化与高剂量 （5 mg/kg/d） 相当。BAT 和 WAT 是代谢紊乱最显著的关键靶组织。BPS 通过减少肉碱载体破坏 WAT 中的脂肪酸β氧化，导致 WAT 脂肪堆积。对 BPS 暴露的抵抗机制表现为 BAT 补偿性产热的动员，其特征是肉碱和 UCP1 表达增加，以及有益共生菌的增加。它们的竞争和不平衡导致了后代的肥胖和胰岛素抵抗，凸显了针对关键代谢物和微生物群的早期干预的潜力。