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首页> 外文期刊>Archives of Toxicology >New mechanistic insights on the metabolic-disruptor role of chlorpyrifos in apoE mice: a focus on insulin- and leptin-signalling pathways
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New mechanistic insights on the metabolic-disruptor role of chlorpyrifos in apoE mice: a focus on insulin- and leptin-signalling pathways

机译：关于紫杉醇鼠紫外线的新机制洞察 - 紫杉鼠中的作用：对胰岛素和瘦素信号通路的关注

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Recently, we have provided evidence, suggesting that mice expressing the human apolipoprotein E3 (apoE3) are more prone to develop an obesity-like phenotype and a diabetic profile when subchronically fed a chlorpyrifos (CPF)-supplemented diet. The aim of the current study was to examine the underlying mechanisms through which CPF alters both insulin- and leptin-signalling pathways in an APOE-dependent manner. Both adult apoE3- and E4-targeted replacement and C57BL/6 mice were exposed to CPF at 0 or 2 mg/kg body weight/day through the diet for 8 consecutive weeks. We determined the expression of JAK2, p-JAK2, STAT3, p-STAT3, SOCS3, IRS-1, p-IRS-1, AKT, p-AKT, GSK3 beta, p-GSK3 beta, and apoE in the liver, as well as hepatic mRNA levels of pon1, pon2, and pon3. CPF markedly disrupted both leptin and insulin homeostasis, particularly in apoE3 mice. Indeed, only CPF-fed apoE3 mice exhibited an increased phosphorylation ratio of STAT3, as well as increased total SOCS3 protein levels. Similarly, the exposure to CPF drastically reduced the phosphorylation ratio of both AKT and GSK3 beta, especially in apoE3 mice. Overall, CPF reduced the expression of the three pon genes, principally in C57BL/6 and apoE3 mice. These results provide notable mechanistic insights on the metabolic effects of the pesticide CPF, and attest the increased vulnerability of apoE3 carriers to its metabolic-disruptor role.
机译：最近，我们提供了证据，表明表达人载脂蛋白E3（APOE3）的小鼠更容易发生肥胖样表型，当时喂食紫外线（CPF）饮食时。目前研究的目的是检查CPF以APOE依赖性方式改变胰岛素和瘦素信号通路的潜在机制。将成人3-和E4靶向替代物和C57BL / 6小鼠在连续8周连续8周暴露于0或2mg / kg体重/天的CPF。我们确定了JAK2，P-JAK2，STAT3，P-STAT3，SOCS3，IRS-1，P-IRS-1，AKT，P-AKT，GSK3β，P-GSK3β和Apoe的表达，如以及PON1，PON2和PON3的肝mRNA水平。 CPF显着破坏了瘦素和胰岛素稳态，特别是在ApoE3小鼠中。实际上，只有CPF喂养的apoE3小鼠表现出含有STAT3的磷酸化比例，以及增加的SOCS3蛋白水平。类似地，暴露于CPF大大降低了AKT和GSK3β的磷酸化比，尤其是在ApoE3小鼠中。总体而言，CPF减少了三个PON基因的表达，主要是在C57BL / 6和APOE3小鼠中。这些结果为农药CPF的代谢效应提供了显着的机械洞察，并证明了APOE3载体对其代谢破坏的作用的增加脆弱性。

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