In vitro effects of emerging bisphenols on myocyte differentiation and insulin responsiveness.
In vitro effects of emerging bisphenols on myocyte differentiation and insulin responsiveness.
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DOI：
10.1093/toxsci/kfaa130
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发表时间：
2020-08
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影响因子：
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通讯作者：
Jiongjie Jing;Y. Pu;A. Veiga-Lopez;L. Lyu
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作者：
Jiongjie Jing;Y. Pu;A. Veiga-Lopez;L. Lyu
双酚是人类普遍接触的内分泌干扰化学物质。产前接触双酚 A (BPA) 可导致胰岛素抵抗。然而，其他新兴双酚，如双酚 S (BPS) 和双酚 F (BPF) 的代谢影响却鲜为人知。由于骨骼肌是最大的胰岛素靶组织，本研究的目的是评估两种新兴双酚（BPS 和 BPF）对骨骼肌细胞的细胞毒性、增殖、肌源性分化和胰岛素反应性的影响。我们在 C2C12 小鼠和 L6 大鼠成肌细胞系中使用剂量反应方法对此进行了测试。结果表明，与 L6 大鼠成肌细胞相比，C2C12 小鼠成肌细胞对双酚更敏感。在这两种细胞系中，BPA 的细胞毒性更强，其次是 BPF 和 BPS。暴露于 10-4 M 剂量的 BPF 后，C2C12 成肌细胞增殖较高，暴露于超过 10-10 M 剂量的 BPF 或 BPS 后，融合指数增加。暴露于 BPS 和 BPF 还降低了 p-AKT (Thr) 和 p-GSK-3β 的基线表达，但不降低 mTOR 和 GLUT4 等下游效应子。总之，在非细胞毒性剂量下，BPS 和 BPF 可以改变成肌细胞增殖、分化，并部分调节胰岛素受体信号通路的早期效应器。然而，此处评估的 BPS 或 BPF 短期暴露不会导致胰岛素反应性受损。
Bisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A (BPA) exposure can lead to insulin resistance. However, the metabolic effects of other emerging bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF) are less understood. Since the skeletal muscle is the largest of the insulin target tissues, the goal of this study was to evaluate the effects of two emerging bisphenols (BPS and BPF) on cytotoxicity, proliferation, myogenic differentiation, and insulin responsiveness in skeletal muscle cells. We tested this using a dose-response approach in C2C12 mouse and L6 rat myoblast cell lines. The results showed that C2C12 mouse myoblasts were more susceptible to bisphenols compared to L6 rat myoblasts. In both cell lines, BPA was more cytotoxic, followed by BPF and BPS. C2C12 myoblast proliferation was higher upon BPF exposure at the 10-4 M dose and the fusion index was increased after exposure to either BPF or BPS at doses over 10-10 M. Exposure to BPS and BPF also reduced baseline expression of p-AKT (Thr) and p-GSK-3β, but not downstream effectors such as mTOR and GLUT4. In conclusion, at non-cytotoxic doses, BPS and BPF can alter myoblast cell proliferation, differentiation and partially modulate early effectors of the insulin receptor signaling pathway. However, BPS or BPF short-term exposure evaluated here does not result in impaired insulin responsiveness.