College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China; School of Environmental Sciences and Engineering, Shandong University, Qingdao, 266237, Shandong Province, China.
College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong Province, China.
Aquat Toxicol. 2021 Dec;241:106000. doi: 10.1016/j.aquatox.2021.106000. Epub 2021 Oct 19.
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，已在各种环境介质中频繁检出，包括人体中，并成为一种新兴污染物。最近的流行病学研究表明，暴露于 BPAF 会导致人类糖尿病的发病率增加，这表明 BPAF 可能是一种潜在的致糖尿病内分泌干扰物。然而，BPAF 暴露对动物葡萄糖稳态的影响及其潜在机制在很大程度上仍不清楚，这可能限制了我们对 BPAF 健康风险的理解。为此，斑马鱼（Danio rerio）作为研究动物糖代谢和糖尿病的新兴且有价值的模型，被暴露于环境相关浓度（5 和 50μg/L）和 500μg/L 的 BPAF 中 28 天。在我们的研究中检测到了几个与血糖代谢相关的关键毒性终点，结果显示 BPAF 暴露组的空腹血糖水平、肝糖原含量和肝体比显著升高，肌肉糖原含量显著降低。实时定量 PCR 的结果显示，参与糖代谢网络的基因表达异常，这可能促进了肝脏的糖异生，抑制了肌肉和/或肝脏中的糖生成和糖酵解。此外，胰岛素调节的失败，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 诱导的糖代谢功能障碍的潜在机制。总之，我们的研究结果提供了新的体内证据，表明 BPAF 通过干扰糖代谢网络导致空腹高血糖，强调了环境暴露于 BPAF 诱发糖尿病的潜在健康风险。
