在小鼠中,PFOA和与PFOS同时暴露会诱导AMPK依赖的低血糖症:来自生理学,多组学和分子对接的综合证据
Chang Jiajun1, Xu Xiaojuan2, Chen Shiyan3
1Key Laboratory of Yangtze River Water Environment, College of Environmental Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, 1239 Siping Road, Shanghai 200092, China.
和多醇基物质 (PFAS),如PFOA和PFOS,可以破坏葡萄糖代谢. 这项研究表明,PFAS暴露会导致低血糖症,因为它通过皮菌素受体影响AMPK信号通路.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 代谢生物化学 代谢生物化学
背景情况:
- 和多基基物质 (PFAS) 是持久的环境污染物.
- 越来越多的证据将PFAS与代谢毒性联系在一起,但对葡萄糖平衡的影响尚不清楚.
研究的目的:
- 研究 perfluorooctanoic 酸 (PFOA) 和 perfluorooctane 硫酸盐 (PFOS) 对葡萄糖平衡的作用.
- 阐明PFAS诱导的代谢干扰的潜在分子机制.
主要方法:
- 雄性C57BL/6小鼠在28天内暴露在PFOA,PFOS或两者之间.
- 评估的生理指标 (禁食血糖,肝脏葡萄糖).
- 进行了转录组,代谢组和分子对接分析.
主要成果:
- 同时暴露于PFOA和PFOS引起低血糖症和肝脏糖原减少.
- 确定AMPK信号通路作为葡萄糖代谢中断的中心调解者.
- 显示PFOA/PFOS与阿迪波内克丁受体 (AdipoR1/2) 结合,抑制AMPK激活.
结论:
- 为PFAS诱导的葡萄糖代谢中断建立了一个AdipoR1/2-AMPK介导的机制.
- 相关的PFAS暴露,特别是PFOA或共同暴露,导致AMPK依赖的低血糖症.
- 强调需要评估环境PFAS混合物的代谢健康风险.
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