Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice:: a proteomics approach
Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice:: a proteomics approach
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DOI：
10.1096/fj.05-3953fje
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发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Roche, HM
中科院分区：
文献类型：
--
作者：
de Roos, B;Rucklidge, G;Roche, HM
共轭亚油酸（CLA）影响动脉粥样硬化形成，但其机制尚不清楚。我们探讨了两种异构体的共轭亚油酸，顺式9，反式11-共轭亚油酸和反式10，顺式12-共轭亚油酸，影响脂质和葡萄糖代谢，以及肝脏蛋白质的表达，在载脂蛋白E基因敲除小鼠。干预12周后，血浆甘油三酯，NEFA，葡萄糖浓度显着较高的trans 10，cis 12-CLA组，而血浆甘油三酯，NEFA，葡萄糖，胰岛素浓度显着较低的cis 9，trans 11- CLA组，与对照小鼠消耗亚油酸。蛋白质组学发现，两种CLA异构体均可显着上调或下调113种肝脏胞浆蛋白。主成分分析表明，cis 9，trans 11- CLA的治疗作用主要是通过上调热休克蛋白70 kD的不同翻译后形式来解释的。相反，trans 10，cis 12-CLA的治疗效果主要通过上调促炎、β-氧化和生酮途径中的关键酶来解释。相关性分析再次强调了两种CLA异构体对不同途径的不同影响，但也揭示了胰岛素抵抗和肝血清转铁蛋白水平升高之间的联系。因此，我们的系统生物学方法提供了新的见解的机制，个别CLA异构体差异影响动脉粥样硬化相关的途径，如胰岛素抵抗和炎症。
Conjugated linoleic acids (CLA) affect atherogenesis, but mechanisms are not well understood. We explored how two isomers of CLA, cis9, trans11- CLA and trans10, cis12-CLA, affected lipid and glucose metabolism, as well as hepatic protein expression, in apolipoprotein E knockout mice. After 12 wk of intervention, plasma triglyceride, NEFA, and glucose concentrations were significantly higher in the trans10, cis12-CLA group, whereas plasma triglyceride, NEFA, glucose, and insulin concentrations were significantly lower in the cis9, trans11- CLA group, compared with control mice consuming linoleic acid. Proteomics identified significant up- or down-regulation of 113 liver cytosolic proteins by either CLA isomer. Principal component analysis revealed that the treatment effect of cis9, trans11- CLA was mainly explained by the up- regulation of different posttranslational forms of heat shock protein 70 kD. In contrast, the treatment effect of trans10, cis12-CLA was mainly explained by up- regulation of key enzymes in the gluconeogenic, beta-oxidation, and ketogenesic pathways. Correlation analysis again emphasized the divergent effects of both CLA isomers on different pathways, but also revealed a linkage between insulin resistance and increased levels of hepatic serotransferrin. Thus, our systems biology approach provided novel insights into the mechanisms by which individual CLA isomers differentially affect pathways related to atherogenesis, such as insulin resistance and inflammation.