Bisphenol AF (BPAF), one of the main alternatives to bisphenol A, has been frequently detected in various environmental media, including the human body, and is an emerging contaminant. Epidemiological investigations have recently shown the implications of exposure to BPAF in the incidence of diabetes mellitus in humans, indicating that BPAF may be a potential diabetogenic endocrine disruptor. However, the effects of BPAF exposure on glucose homeostasis and their underlying mechanisms in animals remain largely unknown, which may limit our understanding of the health risks of BPAF. To this end, zebrafish (Danio rerio), an emerging and valuable model in studying animal glycometabolism and diabetes, were exposed to environmentally relevant concentrations (5 and 50 μg/L) and 500 μg/L BPAF for 28 d. Several key toxicity endpoints of blood glucose metabolism were detected in our study, and the results showed significantly increased fasting blood glucose levels, hepatic glycogen contents and hepatosomatic indexes and decreased muscular glycogen contents in the BPAF-exposed zebrafish. The results of quantitative real-time PCR showed the abnormal expression of genes involved in glycometabolic networks, which might promote hepatic gluconeogenesis and inhibit glycogenesis and glycolysis in the muscle and/or liver. Furthermore, the failure of insulin regulation, including plasma insulin deficiency and impaired insulin signaling pathways in target tissues, may be a potential mechanism underlying BPAF-induced dysfunctional glycometabolism. In summary, our results provide novel in vivo evidence that BPAF can cause fasting hyperglycemia by interfering with glycometabolic networks, which emphasizes the potential health risks of environmental exposure to BPAF in inducing diabetes mellitus.

双酚 AF (BPAF) 是双酚 A 的主要替代品之一，经常在包括人体在内的各种环境介质中检测到，并且是一种新兴的污染物。最近的流行病学调查表明，BPAF 暴露对人类糖尿病发病率的影响，表明 BPAF 可能是潜在的致糖尿病内分泌干扰物。然而，BPAF 暴露对动物体内葡萄糖稳态的影响及其潜在机制在很大程度上仍然未知，这可能会限制我们对 BPAF 健康风险的理解。为此，斑马鱼（Danio rerio) 是研究动物糖代谢和糖尿病的新兴且有价值的模型，暴露于环境相关浓度（5 和 50 μg/L）和 500 μg/L BPAF 28 天。在我们的研究中检测了血糖代谢的几个关键毒性终点，结果显示暴露于 BPAF 的斑马鱼的空腹血糖水平、肝糖原含量和肝体指数显着增加，肌糖原含量降低。实时定量 PCR 的结果显示参与糖代谢网络的基因表达异常，这可能促进肝脏糖异生并抑制肌肉和/或肝脏中的糖生成和糖酵解。此外，胰岛素调节失败，包括血浆胰岛素缺乏和靶组织中胰岛素信号通路受损，可能是 BPAF 引起的糖代谢障碍的潜在机制。总之，我们的结果提供了新颖的体内证据表明 BPAF 可通过干扰糖代谢网络引起空腹高血糖，这强调了环境暴露于 BPAF 诱发糖尿病的潜在健康风险。