Targeted metabolomics reveals that 2,3,7,8-tetrachlorodibenzofuran exposure induces hepatic steatosis in male mice.
Targeted metabolomics reveals that 2,3,7,8-tetrachlorodibenzofuran exposure induces hepatic steatosis in male mice.
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靶向代谢组学揭示，2,3,7,8-四氯二苯并呋喃暴露会诱导雄性小鼠肝脂肪变性。
DOI：
10.1016/j.envpol.2019.113820
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发表时间：
2019-12
影响因子：
8.9
通讯作者：
Zhang Limin
中科院分区：
文献类型：
--
作者：
Yuan Pei-Hong;Dong Manyuan;Lei Hehua;Xu Guangyong;Chen Gui;Song Yuchen;Ma Jianfeng;Cheng Liming;Zhang Limin
2，3，7，8-四氯二苯并呋喃（TCDF）是城市垃圾焚烧产生的典型持久性有机污染物（POPs）之一，其环境暴露对人体健康具有毒性作用。本研究主要采用靶向代谢组学和非靶向1H NMR代谢组学相结合的方法研究TCDF暴露对小鼠脂质稳态的影响。我们发现TCDF暴露诱导肝脏脂肪生成，这是非酒精性脂肪性肝病的早期阶段，表现为过量的脂质，包括甘油三酯、脂肪酸和脂毒性神经酰胺在肝脏中积累，以及通过激活芳烃受体（AHR）及其靶基因如Cyp 1a 1和Cd 36而升高的血清极低密度脂蛋白。我们还发现TCDF暴露诱导小鼠肝脏中磷脂和胆碱代谢产物以及内质网（ER）标记物的改变，表明宿主细胞膜结构完整性和ER应激的破坏导致肝脏脂肪变性。此外，还从组织病理学评估和生物测定中获得了补充信息，强烈支持TCDF的毒性作用。这些结果为TCDF毒性与脂肪肝疾病相关提供了新的证据，并进一步加深了我们对环境污染物暴露对健康影响的理解。
Environmental exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF), one of typical persistent organic pollutants (POPs) produced from municipal waste combustion, exerts toxic effects on human healthy. In the current study, we mainly used targeted metabolomics combined with untargeted1H NMR-based metabolomics to investigate the effects of TCDF exposure on lipid homeostasis in mice. We found that TCDF exposure induced hepatic lipogenesis, the early-stage of non-alcoholic fatty liver disease, manifested by excessive lipids including triglycerides, fatty acids and lipotoxic ceramides accumulated in the liver together with elevated serum very low-density lipoprotein by activating the aryl hydrocarbon receptor (AHR) and its target genes such asCyp1a1andCd36. We also found that TCDF exposure induced alteration of phospholipids and choline metabolites and endoplasmic reticulum (ER) markers in the liver of mice, indicating that disruption of host cell membrane structural integrity and ER stress leading to hepatic steatosis. In addition, complementary information was also obtained from histopathologic assessments and biological assays, strongly supporting toxic effects of TCDF. These results provide new evidence of TCDF toxicity associated with fatty liver disease and further our understanding of health effects of environmental pollutants exposure.
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影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
影响因子：
9.3
作者：
Holm, PI;Ueland, PM;Lien, EA
通讯作者：
Lien, EA
影响因子：
3.2
作者：
Dalton, T P;Kerzee, J K;Puga, A
通讯作者：
Puga, A
DOI：
10.1172/jci24930
发表时间：
2005-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
S. Tamura;I. Shimomura
通讯作者：
S. Tamura;I. Shimomura
影响因子：
11.4
作者：
M. Harnly;R. Stephens;C. McLaughlin;J. Marcotte;Myrto X Petreas;L. Goldman
通讯作者：
M. Harnly;R. Stephens;C. McLaughlin;J. Marcotte;Myrto X Petreas;L. Goldman