Metabolomic analysis of the effects of polychlorinated biphenyls in nonalcoholic fatty liver disease.
Metabolomic analysis of the effects of polychlorinated biphenyls in nonalcoholic fatty liver disease.
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DOI：
10.1021/pr300297z
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发表时间：
2012-07-06
影响因子：
4.4
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Shi X;Wahlang B;Wei X;Yin X;Falkner KC;Prough RA;Kim SH;Mueller EG;McClain CJ;Cave M;Zhang X
多氯联苯（PCBs）是一种持久性有机污染物，在流行病学研究中与肝酶异常、疑似非酒精性脂肪性肝病（NAFLD）、肥胖和代谢综合征有关。在对人体接触多氯联苯的流行病学调查中，多氯联苯153在多氯联苯同系物中的血清浓度最高。为了确定PCB 153对小鼠肝脏的影响，C57 BL/6 J小鼠被喂食对照饮食（CD）或高脂肪饮食（HFD）12周，有或没有PCB 153共同暴露。采用线性阱四重傅里叶变换离子回旋共振质谱仪（LTQ-FTICR MS）通过直接注入纳米电喷雾电离（DI-nESI）质谱法分析小鼠肝脏中的代谢物提取物。代谢组学分析表明，喂食暴露于PCB 153的对照饮食（CD+PCB 153）的小鼠和喂食不暴露于PCB 153的对照饮食（CD）的小鼠之间的代谢特征没有差异。然而，与CD组相比，喂食HFD的小鼠中10种代谢物的水平升高，15种代谢物的水平降低。与CD+PCB 153组相比，高脂饲料+PCB 153组（HFD+PCB 153组）有6种代谢物的丰度增加，18种代谢物的丰度减少。与HFD组相比，HFD+PCB 153组有2种代谢物的丰度增加，12种代谢物的丰度减少。这些观察结果与组织学结果一致，表明PCB 153的代谢效应高度依赖于大量营养素与HFD的相互作用。抗氧化剂消耗可能是这种相互作用的重要后果，因为这种代谢紊乱以前与肥胖和NAFLD有关。
Polychlorinated Biphenyls (PCBs) are persistent organic pollutants and have been associated with abnormal liver enzymes and suspected non-alcoholic fatty liver disease (NAFLD), obesity, and the metabolic syndrome in epidemiological studies. In epidemiological surveys of human PCB exposure, PCB 153 has the highest serum levels among PCB congeners. To determine the hepatic effects of PCB 153 in mice, C57BL/6J mice were fed either a control diet (CD) or a high fat diet (HFD) for 12 weeks, with or without PCB 153 co-exposure. The metabolite extracts from mouse livers were analyzed using linear trap quadruple - Fourier transform ion cyclotron resonance mass spectrometer (LTQ-FTICR MS) via direct infusion nano-electrospray ionization (DI-nESI) mass spectrometry. The metabolomics analysis indicated no difference in the metabolic profile between mice fed the control diet with PCB 153 exposure (CD+PCB 153) and mice fed the control diet (CD) without PCB 153 exposure. However, compared with CD group, levels of 10 metabolites were increased and 15 metabolites were reduced in mice fed HFD. Moreover, compared to CD+PCB 153 group, the abundances of 6 metabolites were increased and 18 metabolites were decreased in the mice fed high fat diet with PCB 153 exposure (HFD+PCB 153). Compared with HFD group, the abundances of 2 metabolites were increased and of 12 metabolites were reduced in HFD+PCB 153 group. These observations agree with the histological results and indicate that the metabolic effects of PCB 153 were highly dependent on macronutrient interactions with HFD. Antioxidant depletion is likely to be an important consequence of this interaction, as this metabolic disturbance has previously been implicated in obesity and NAFLD.
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