Alterations in cellular lipid metabolism produce neutral lipid accumulation following exposure to the organochlorine compound trans-nonachlor in rat primary hepatocytes.
Alterations in cellular lipid metabolism produce neutral lipid accumulation following exposure to the organochlorine compound trans-nonachlor in rat primary hepatocytes.
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DOI：
10.1002/tox.22583
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发表时间：
2018-09
影响因子：
4.5
通讯作者：
Young D
中科院分区：
文献类型：
--
作者：
Howell GE 3rd;McDevitt E;Henein L;Mulligan C;Young D
最近的流行病学研究表明，接触有机氯农药与代谢综合征的发生之间存在显著的正相关关系，越来越多的动物研究支持两者之间的因果关系。然而，连接OC化合物暴露和代谢功能障碍的细胞机制仍然是难以捉摸的。因此，本研究旨在确定直接暴露于三种高度相关的OC化合物是否会促进肝脏脂肪变性，即代谢综合征的肝分支。首先，在新分离的大鼠原代肝细胞中测定了p，p ' -二氯二苯二氯乙烯（DDE），氧氯丹和反式壬氯胺的脂肪变性作用。暴露于反式无氯显着增加中性脂质积累相对于DDE和氧氯丹。为了确定控制脂肪酸可用性增加的可能机制，我们探索了反式非草胺暴露对脂肪酸摄取、新生脂肪生成、甘油三酯分泌和脂肪酸氧化的影响。反式壬草胺没有显著改变脂肪酸摄取。然而，胰岛素刺激的新生脂肪生成以及脂肪酸合成酶的基础表达（脂肪生成的主要调节因子）在反式非草胺暴露后显著增加。有趣的是，暴露于反式无氯后脂肪酸氧化显著减少。脂肪酸氧化的减少伴随着油酸诱导的细胞甘油三酯分泌的轻微但显著的增加。因此，综上所述，目前的数据表明，直接暴露于反式甲草胺比暴露于DDE或氧氯丹具有更强的促脂肪变性作用。反式非草胺的这种促脂肪变性作用似乎主要是通过增加新生脂肪生成和减少脂肪酸氧化介导的。
Recent epidemiological studies have revealed significant positive associations between exposure to organochlorine (OC) pesticides and occurrence of the metabolic syndrome and there are a growing number of animal based studies to support causality. However, the cellular mechanisms linking OC compound exposure and metabolic dysfunction remain elusive. Therefore, the present study was designed to determine if direct exposure to three highly implicated OC compounds promoted hepatic steatosis, the hepatic ramification of the metabolic syndrome. First, the steatotic effect of p,p′-dichlorodiphenyldichloroethylene (DDE), oxychlordane, and trans-nonachlor was determined in freshly isolated rat primary hepatocytes. Exposure to trans-nonachlor significantly increased neutral lipid accumulation as opposed to DDE and oxychlordane. To determine possible mechanisms governing increased fatty acid availability, the effects of trans-nonachlor exposure on fatty acid uptake, de novo lipogenesis, triglyceride secretion, and fatty acid oxidation were explored. Trans-nonachlor did not significantly alter fatty acid uptake. However, insulin-stimulated de novo lipogenesis as well as basal expression of fatty acid synthase, a major regulator of lipogenesis were significantly increased following trans-nonachlor exposure. Interestingly, there was a significant decrease in fatty acid oxidation following trans-nonachlor exposure. This decrease in fatty acid oxidation was accompanied by a slight, but significant increase in oleic acid-induced cellular triglyceride secretion. Therefore, taken together, the present data indicate direct exposure to trans-nonachlor has a more potent pro-steatotic effect than exposure to DDE or oxychlordane. This pro-steatotic effect of trans-nonachlor appears to be predominately mediated via increased de novo lipogenesis and decreased fatty acid oxidation.
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影响因子：
10.4
作者：
Dewailly, É;Mulvad, G;Hansen, JC
通讯作者：
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影响因子：
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作者：
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影响因子：
4.6
作者：
Liu Q;Wang Q;Xu C;Shao W;Zhang C;Liu H;Jiang Z;Gu A
通讯作者：
Gu A
影响因子：
10.4
作者：
Baker NA;Karounos M;English V;Fang J;Wei Y;Stromberg A;Sunkara M;Morris AJ;Swanson HI;Cassis LA
通讯作者：
Cassis LA