Lipid metabolism disorders contribute to hepatotoxicity of triclosan in mice
Lipid metabolism disorders contribute to hepatotoxicity of triclosan in mice
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脂质代谢紊乱导致三氯生对小鼠的肝毒性
DOI：
10.1016/j.jhazmat.2019.121310
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发表时间：
2020-02-15
影响因子：
13.6
通讯作者：
Cai, Zongwei
中科院分区：
文献类型：
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作者：
Huang, Wei;Xie, Peisi;Cai, Zongwei
以往的体内暴露研究主要集中在参与三氯生肝毒性的核受体上。由于肝脏在代谢过程中起着至关重要的作用，脂质代谢失调已被确定为发病机制的潜在驱动因素。研究脂质代谢的变化可能会扩大我们对肝脏毒理学效应的理解以及发生在肝脏的潜在机制。在本研究中，我们综合评估了TCS暴露对小鼠肝脏脂质代谢的影响。我们的研究结果表明，TCS通过上调脂肪酸摄取和新脂肪酸合成来诱导肝脏游离脂肪酸池的显著变化。此外，TCS暴露组小鼠肝脏脂质水平（包括酰基肉碱（AcCa）、神经酰胺（Cer）、甘油三酯（TG）、磷脂酰胆碱（PC）、溶血磷脂酰胆碱（LPC）、磷脂酰乙醇胺（PE））升高，与TG合成、脂肪酸氧化和炎症相关基因上调。这些脂质稳态的变化可能导致膜不稳定、脂质积累、氧化应激和炎症。我们的研究结果表明，TCS暴露可诱导小鼠肝脏脂质代谢紊乱，这将进一步促进TCS的肝损伤作用。
Previous in vivo exposure studies focused mainly on nuclear receptors involved in hepatotoxicity of triclosan (TCS). As liver plays a vital role in metabolic processes, dysregulations in lipid metabolism have been identified as potential drivers of pathogenesis. Investigation of changes in lipid metabolism might widen our understanding of toxicological effects as well as the underlying mechanism occurring in the liver. In this study, we comprehensively assessed the effect of TCS exposure on hepatic lipid metabolism in mice. Our results showed that TCS induced significant changes in hepatic free fatty acid pool by upregulation of fatty acid uptake and de novo fatty acid synthesis. Besides, hepatic levels of lipids, including acyl carnitine (AcCa), ceramide (Cer), triacylglycerols (TG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE) were also increased, together with upreguation of genes associated to TG synthesis, fatty acid oxidation and inflammation in TCS exposure group. These changes in lipid homeostasis could contribute to membrane instability, lipid accumulation, oxidative stress and inflammation. Our results suggested that TCS exposure could induce hepatic lipid metabolism disorders in mice, which would further contribute to the liver damage effects of TCS.