Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC), associated with obesity and insulin resistance. The FDA prohibited the use of BPA-based polycarbonate resins in infant formula packaging; thus, its analogs, viz. Bisphenol S (BPS) and Bisphenol F (BPF) were considered alternatives in epoxy resins, plastics, and food cans. As these analogs might evoke a similar response, we investigated the role of Bisphenols (BPA, BPF, and BPS), on insulin signaling in CHO-HIRc-myc-GLUT4eGFP cells at environmentally relevant concentrations of 2 nM and 200 nM. Insulin signaling demonstrated that Bisphenols reduced phosphorylation of IR and AKT2, GLUT4 translocation, and glucose uptake. This was accompanied by increased oxidative stress. Furthermore, SWATH-MS-based proteomics of 3T3-L1 cells demonstrated that Bisphenol-treated cells regulate proteins in insulin resistance, adipogenesis, and fatty acid metabolism pathways differently. All three Bisphenols induced differentially expressed proteins enriched similar pathways, although their abundance differed for each Bisphenol. This might be due to their varying toxicity level, structural differences, and estrogen-mimetic activity. This study has important implications in addressing health concerns related to EDCs. Given that the analogs of BPA are considered alternatives to BPA, the findings of this study suggest they are equally potent in altering fatty acid metabolism and inducing insulin resistance.

中文翻译：

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SWATH-MS 揭示双酚 A 及其类似物调节导致胰岛素信号传导和脂肪酸代谢破坏的途径

双酚 A (BPA) 是一种内分泌干扰化学物质 (EDC)，与肥胖和胰岛素抵抗有关。 FDA禁止在婴儿配方奶粉包装中使用基于BPA的聚碳酸酯树脂；因此，它的类似物，即。双酚 S (BPS) 和双酚 F (BPF) 被认为是环氧树脂、塑料和食品罐头的替代品。由于这些类似物可能引起类似的反应，我们研究了环境相关浓度 2 nM 和 200 nM 的双酚（BPA、BPF 和 BPS）对 CHO-HIRc-myc-GLUT4eGFP 细胞中胰岛素信号传导的作用。胰岛素信号传导表明双酚可减少 IR 和 AKT2 的磷酸化、GLUT4 易位和葡萄糖摄取。这伴随着氧化应激的增加。此外，基于 SWATH-MS 的 3T3-L1 细胞蛋白质组学表明，双酚处理的细胞以不同的方式调节胰岛素抵抗、脂肪生成和脂肪酸代谢途径中的蛋白质。所有三种双酚诱导差异表达的蛋白质富集相似的途径，尽管每种双酚的丰度不同。这可能是由于它们的毒性水平不同、结构差异和雌激素模拟活性不同。这项研究对于解决与 EDC 相关的健康问题具有重要意义。鉴于 BPA 类似物被认为是 BPA 的替代品，这项研究的结果表明它们在改变脂肪酸代谢和诱导胰岛素抵抗方面同样有效。