Cetyl Alcohol Polyethoxylates Disrupt Metabolic Health in Developmentally Exposed Zebrafish.

Cetyl Alcohol Polyethoxylates Disrupt Metabolic Health in Developmentally Exposed Zebrafish.
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DOI:
10.3390/metabo13030359
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发表时间:
2023-02-28
期刊:
影响因子:
4.1
通讯作者:
Kassotis CD
Kassotis CD
中科院分区:
生物学3区
文献类型:
--
作者:
LeFauve MK;Bérubé R;Heldman S;Chiang YT;Kassotis CD

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醇聚氧乙烯酸酯(AEOS),如十六醇聚氧乙烯醚(CetAEO),是一种高产量的表面活性剂,用于洗衣粉、硬表面清洁剂、农药配方、纺织生产、石油、涂料和其他产品。AEOS已被认为是烷基酚聚氧乙烯醚(APEO)的低毒替代品,如壬基酚和辛基酚聚氧乙烯酸酯。我们先前证明,在几种体外成脂模型中,壬基酚聚氧乙烯醚诱导甘油三酯的积累,并促进发育中暴露的斑马鱼的肥胖和体重增加。我们还证明,在小鼠前脂肪细胞模型中,不同的APEO和AEOS能够增加甘油三酯的积累和/或前脂肪细胞的增殖。因此,这项研究的目标是评估CetAEO促进肥胖和改变发育中暴露的斑马鱼(Danio Rerio)的生长和/或发育(毒性、长度、体重、行为、能量消耗)的潜力。我们还试图通过询问不同链长的CetAEO来扩大我们对乙氧基酸酯链长依赖效应的理解。我们在两个不同的人骨髓间充质干细胞模型和小鼠前脂肪细胞模型中显示了一致的成脂作用。在斑马鱼接触化学物质后,我们立即报告了神经发育中断和在明/暗活动测试中的异常行为,中等链长的CetAEO暴露的鱼在明暗两个阶段都表现出多动。到了第30天,我们证明了十六醇和十六烷基三乙醇胺扰乱了发育中暴露的斑马鱼的脂肪沉积,尽管对标准长度或毛重没有明显影响。这项研究表明这些常见环境污染物的代谢健康问题,表明进一步需要评估分子机制,并更好地表征环境浓度,以进行人类健康风险评估。
Alcohol polyethoxylates (AEOs), such as cetyl alcohol ethoxylates (CetAEOs), are high-production-volume surfactants used in laundry detergents, hard-surface cleaners, pesticide formulations, textile production, oils, paints, and other products. AEOs have been suggested as lower toxicity replacements for alkylphenol polyethoxylates (APEOs), such as the nonylphenol and octylphenol polyethoxylates. We previously demonstrated that nonylphenol polyethoxylates induced triglyceride accumulation in several in vitro adipogenesis models and promoted adiposity and increased body weights in developmentally exposed zebrafish. We also demonstrated that diverse APEOs and AEOs were able to increase triglyceride accumulation and/or pre-adipocyte proliferation in a murine pre-adipocyte model. As such, the goals of this study were to assess the potential of CetAEOs to promote adiposity and alter growth and/or development (toxicity, length, weight, behavior, energy expenditure) of developmentally exposed zebrafish (Danio rerio). We also sought to expand our understanding of ethoxylate chain-length dependent effects through interrogation of varying chain-length CetAEOs. We demonstrated consistent adipogenic effects in two separate human bone-marrow-derived mesenchymal stem cell models as well as murine pre-adipocytes. Immediately following chemical exposures in zebrafish, we reported disrupted neurodevelopment and aberrant behavior in light/dark activity testing, with medium chain-length CetAEO-exposed fish exhibiting hyperactivity across both light and dark phases. By day 30, we demonstrated that cetyl alcohol and CetAEOs disrupted adipose deposition in developmentally exposed zebrafish, despite no apparent impacts on standard length or gross body weight. This research suggests metabolic health concerns for these common environmental contaminants, suggesting further need to assess molecular mechanisms and better characterize environmental concentrations for human health risk assessments.
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