In Vitro Effects of Emerging Bisphenols on Myocyte Differentiation and Insulin Responsiveness

Bisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A 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. Because the skeletal muscle is the largest of the insulin target tissues, the goal of this study was to evaluate the effects of 2 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 with L6 rat myoblasts. In both cell lines, bisphenol A 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 glucose transporter-4. In conclusion, at noncytotoxic 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.