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跨组学分析揭示环境细颗粒物暴露对雌性小鼠肝脏代谢的影响。

Cross-Omics Analyses Reveal the Effects of Ambient PM Exposure on Hepatic Metabolism in Female Mice.

作者信息

Yan Ruifeng, Ji Shaoyang, Ku Tingting, Sang Nan

机构信息

College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan 030006, China.

出版信息

Toxics. 2024 Aug 13;12(8):587. doi: 10.3390/toxics12080587.

Abstract

Ambient particulate matter (PM) is a potential risk factor for metabolic damage to the liver. Epidemiological studies suggest that elevated PM concentrations cause changes in hepatic metabolism, but there is a lack of laboratory evidence. Here, we aimed to evaluate the effects of PM exposure on liver metabolism in C57BL/6j female mice (10 months old) and to explore the mechanisms underlying metabolic alterations and differential gene expressions by combining metabolomics and transcriptomics analyses. The metabolomics results showed that PM exposure notably affected the metabolism of amino acids and organic acids and caused hepatic lipid and bile acid accumulation. The transcriptomic analyses revealed that PM exposure led to a series of metabolic pathway abnormalities, including steroid biosynthesis, steroid hormone biosynthesis, primary bile acid biosynthesis, etc. Among them, the changes in the bile acid pathway might be one of the causes of liver damage in mice. In conclusion, this study clarified the changes in liver metabolism in mice caused by PM exposure through combined transcriptomic and metabolomic analyses, revealed that abnormal bile acid metabolism is the key regulatory mechanism leading to metabolic-associated fatty liver disease (MAFLD) in mice, and provided laboratory evidence for further clarifying the effects of PM on body metabolism.

摘要

环境颗粒物(PM)是肝脏代谢损伤的潜在危险因素。流行病学研究表明,PM浓度升高会导致肝脏代谢发生变化,但缺乏实验室证据。在此,我们旨在评估PM暴露对C57BL/6j雌性小鼠(10月龄)肝脏代谢的影响,并通过整合代谢组学和转录组学分析来探索代谢改变和基因表达差异的潜在机制。代谢组学结果表明,PM暴露显著影响氨基酸和有机酸的代谢,并导致肝脏脂质和胆汁酸积累。转录组分析显示,PM暴露导致一系列代谢途径异常,包括类固醇生物合成、类固醇激素生物合成、初级胆汁酸生物合成等。其中,胆汁酸途径的变化可能是小鼠肝脏损伤的原因之一。总之,本研究通过转录组学和代谢组学联合分析阐明了PM暴露引起的小鼠肝脏代谢变化,揭示了异常胆汁酸代谢是导致小鼠代谢相关脂肪性肝病(MAFLD)的关键调控机制,并为进一步阐明PM对机体代谢的影响提供了实验室证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d196/11360593/f70464a2440c/toxics-12-00587-g001.jpg

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