Multi-omics analysis reveals hepatic lipid metabolism profiles and serum lipid biomarkers upon indoor relevant VOC exposure.
Multi-omics analysis reveals hepatic lipid metabolism profiles and serum lipid biomarkers upon indoor relevant VOC exposure.
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多组学分析揭示了室内相关VOC暴露下的肝脂代谢谱和血清脂质生物标志物。
DOI：
10.1016/j.envint.2023.108221
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发表时间：
2023-09
影响因子：
11.8
通讯作者：
Gan Miao;Yu Wang;Baoqiang Wang;Hongyan Yu;Jing Liu;Ruonan Pan;Chengying Zhou;Jie Ning;Yuxin Zheng;Rong Zhang;Xiaoting Jin
中科院分区：
文献类型：
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作者：
Gan Miao;Yu Wang;Baoqiang Wang;Hongyan Yu;Jing Liu;Ruonan Pan;Chengying Zhou;Jie Ning;Yuxin Zheng;Rong Zhang;Xiaoting Jin
挥发性有机化合物(VOC)作为一种广泛存在的室内空气污染物，对健康造成多种不良影响，尤其是对肝脏的损害，已成为公众日益关注的问题。然而，目前的毒性数据本质上仅限于单一或主要挥发性有机化合物物种。关于真正的室内 VOC 引起的肝损伤的毒性作用、生物标志物和潜在机制的知识有限。本文建立了室内相关VOC暴露模型来评估肝脏不良后果。利用机器学习和多组学方法，包括肝脂质组学、血清脂质组学和肝脏转录组学，揭示了VOC暴露刺激的肝损伤特征、血清脂质生物标志物以及相关机制。结果表明，室内相关VOC导致肝脏脂质代谢异常，主要表现为三酰甘油（TG）及其前体物质二酰甘油（DG）减少，可能导致肝脏不良结局的发生。在血清脂质生物标志物方面，利用机器学习发现了血清中的五种脂质生物标志物，以反映VOC引起的肝脂质紊乱。多组学方法表明，上调的 Dgkq 扰乱了 DG 和磷脂酸 (PA) 的相互转化，导致 TG 下调。深入分析表明VOC下调FoxO转录因子，从而导致Dgkq上调。因此，本研究可以从多组学分析的角度，为理解室内相关VOC暴露模型VOC暴露引起的肝损伤提供有价值的见解。
As a widespread indoor air pollutant, volatile organic compound (VOC) caused various adverse health effects, especial the damage to liver, which has become a growing public concern. However, the current toxic data are intrinsically restricted in the single or major VOC species. Limited knowledge is available regarding toxic effects, biomarkers and underlying mechanisms of real indoor VOC-caused liver damage. Herein, an indoor relevant VOC exposure model was established to evaluate the hepatic adverse outcomes. Machine learning and multi-omics approaches, including liver lipidomic, serum lipidomic and liver transcriptomic, were utilized to uncover the characteristics of liver damage, serum lipid biomarkers, and involved mechanism stimulated by VOC exposure. The result showed that indoor relevant VOC led to the abnormal hepatic lipid metabolism, mainly manifested as a decrease in triacylglycerol (TG) and its precursor substance diacylglycerol (DG), which could be contributed to the occurrence of hepatic adverse outcomes. In terms of serum lipid biomarkers, five lipid biomarkers in serum were uncovered using machine learning to reflect the hepatic lipid disorders induced by VOC. Multi-omics approaches revealed that the upregulatedDgkqdisturbed the interconversion of DG and phosphatidic acid (PA), leading to a TG downregulation. The in-depth analysis revealed that VOC down-regulated FoxO transcription factor, contributing to the upregulation ofDgkq. Hence, this study can provide valuable insights into the understanding of liver damage caused by indoor relevant VOC exposure model VOC exposure, from the perspective of multi-omics analysis.