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脂质组学和转录组学研究微塑料暴露对小鼠肝脏脂质代谢的影响。

Lipidomics and transcriptomics insight into impacts of microplastics exposure on hepatic lipid metabolism in mice.

机构信息

School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, China; Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, 310053, China.

出版信息

Chemosphere. 2022 Dec;308(Pt 3):136591. doi: 10.1016/j.chemosphere.2022.136591. Epub 2022 Sep 24.

DOI:10.1016/j.chemosphere.2022.136591
PMID:36167205
Abstract

Microplastics (MPs), the emerging environmental pollutants, have attracted global attention due to the potential public health challenge and ecological security risk. Recent studies suggested liver as a vulnerable organ to MPs exposure, evidenced by abnormal hepatic lipid metabolism upon MPs intake in multiple animal species. However, the specific changes of lipid metabolism in mammalian livers, as well as the underlying mechanisms, remain to be elucidated. In the present study, C57BL/6 mice were randomly assigned to normal drinking water or drinking water containing 100 μg L or 1000 μg L polystyrene (PS) MPs for 8 weeks. MPs exposure exerted no significant effect on body weight, serum triglyceride or total cholesteryl esters. However, mice showed impaired glucose tolerance and hepatic lipid deposition in response to high-dose MPs administration. Further lipidomic analysis showed significant alteration in hepatic lipid species particularly with free fatty acids (FFAs) and triacylglycerols (TAGs) in mice exposed to MPs. Meanwhile, the liver transcriptional profile indicated MPs exposure-induced differentially expressed genes (DEGs) were enriched in pathways of lipid metabolism and unfolded protein response. Furthermore, most altered lipid species were significantly correlated with DEGs enriched in lipid metabolic signaling. These findings provide lipidomic and transcriptional signatures of liver in response to MPs exposure, which will shed light on further understanding of the metabolic toxicity of MPs.

摘要

微塑料(MPs)作为新兴的环境污染物,由于其对公众健康的潜在挑战和生态安全风险而引起了全球关注。最近的研究表明,肝脏是 MPs 暴露的一个脆弱器官,在多种动物物种中,摄入 MPs 后会导致肝内脂质代谢异常。然而,哺乳动物肝脏中脂质代谢的具体变化以及潜在的机制仍有待阐明。在本研究中,C57BL/6 小鼠被随机分为饮用正常水或含有 100μg/L 或 1000μg/L 聚苯乙烯(PS) MPs 的水 8 周。 MPs 暴露对体重、血清甘油三酯或总胆固醇酯没有显著影响。然而,高剂量 MPs 给药会导致小鼠葡萄糖耐量受损和肝脂质沉积。进一步的脂质组学分析显示,暴露于 MPs 的小鼠肝脏脂质种类发生了显著变化,特别是游离脂肪酸(FFAs)和三酰基甘油(TAGs)。同时,肝脏转录谱表明, MPs 暴露诱导的差异表达基因(DEGs)富集在脂质代谢和未折叠蛋白反应途径中。此外,大多数改变的脂质种类与富含脂质代谢信号的 DEGs 显著相关。这些发现为 MPs 暴露引起的肝脏脂质组学和转录组学特征提供了依据,这将有助于进一步理解 MPs 的代谢毒性。

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