Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae.
Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae.
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DOI：
10.1016/j.envint.2023.107977
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发表时间：
2023-05
影响因子：
11.8
通讯作者：
Yingxin Liu;Shuai Liu;Jing Huang;Yu Liu;Qiyu Wang;Jinyuan Chen;Liwei Sun;W. Tu
中科院分区：
文献类型：
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作者：
Yingxin Liu;Shuai Liu;Jing Huang;Yu Liu;Qiyu Wang;Jinyuan Chen;Liwei Sun;W. Tu
几种全氟烷基和多氟烷基物质（PFAS）与生物体的代谢紊乱有关。然而，很少有研究考虑到它们的综合影响，这将是更有代表性的PFAS发生在环境中。在这项研究中，将斑马鱼胚胎暴露于三种环境相关浓度的18种全氟辛烷磺酸混合物5天，以评估其生物浓缩和代谢后果。在0.5、5和50 μg/L处理组中，斑马鱼幼鱼体内∑PFAS的负荷分别为0.12、1.58和9.63 mg/kg。暴露于PFAS混合物加速孵化和幼虫的心率，增加能量消耗，并降低ATP水平和葡萄糖含量，由于减少摄食量和葡萄糖摄取。代谢组学分析显示，PFAS混合物可促进糖酵解，但抑制磷脂合成，并显著增加脂代谢相关基因（srebf 1、acox和ppar α）的表达，这表明PFAS混合物可促进β-氧化。线粒体膜电位、线粒体内容物和线粒体呼吸链相关基因转录的显著变化（mfn 2，ndufs 1，atp 5 fa 1，andmt-nd 1）与线粒体DNA复制和转录（18 rs-rrn和polg 1）表明，暴露于PFAS混合物可能导致线粒体功能障碍，并进一步破坏葡萄糖和脂质代谢途径，最终导致斑马鱼幼体的代谢紊乱。这些发现表明了评估PFAS混合物对野生动物和人类早期发育的代谢影响的重要性。
Several per- and polyfluoroalkyl substances (PFAS) have been linked to metabolic disorders in organisms. However, few studies have considered their combined effects, which would be more representative of PFAS occurring in the environment. In this study, zebrafish embryos were exposed to a mixture of 18 PFAS at three environmentally relevant concentrations for 5 days to assess their bioconcentration and metabolic consequences. The burdens of ∑PFAS in zebrafish larvae were 0.12, 1.58, and 9.63 mg/kg in the 0.5, 5, and 50 μg/L treatment groups, respectively. Exposure to the PFAS mixture accelerated hatching and larval heart rates, increased energy expenditure, and reduced ATP levels and glucose contents due to decreased feed intake and glucose uptake. Metabolomic analysis revealed that exposure to the PFAS mixture enhanced glycolysis but inhibited phospholipid synthesis, and significantly increased the expression of lipid metabolism related genes (srebf1,acox, andpparα), which indicated enhancedβ-oxidation. The significant changes in mitochondrial membrane potential, mitochondrial content, and the transcription of genes involved in the mitochondrial respiratory chain (mfn2, ndufs1,atp5fa1, andmt-nd1) and mitochondrial DNA replication and transcription (18rs-rrn, andpolg1) suggested that exposure to the PFAS mixture could cause mitochondrial dysfunction and further disrupt glucose and lipid metabolic pathways, ultimately causing metabolic disorders in zebrafish larvae. These findings demonstrate the importance of assessing the metabolic effects of PFAS mixtures on early development in wildlife and humans.