Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach

Baukje De Roos, Garry Jonathan Rucklidge, Martin David Reid, Karen Ross, Gary James Duncan, M A Navarro, J M Arbones-Mainar, M A Guzman-Garcia, J Osada, J Browne, C E Loscher, Helen M. Roche

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    75 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1746-1767
    Number of pages21
    JournalThe FASEB Journal
    Volume19
    Issue number9
    Early online date29 Jul 2005
    DOIs
    Publication statusPublished - Jul 2005

    Keywords

    • dietary fatty acids
    • atherosclerosis
    • glucose metabolism
    • systems biology
    • early aortic atherosclerosis
    • migration inhibitory factor
    • heat-shock-protein
    • lipid-peroxidation
    • fatty-acid
    • hypercholesterol cholesterolemic hamsters
    • lipoprotein metabolism
    • body-composition
    • healthy humans
    • cell-function

    Cite this

    De Roos, B., Rucklidge, G. J., Reid, M. D., Ross, K., Duncan, G. J., Navarro, M. A., Arbones-Mainar, J. M., Guzman-Garcia, M. A., Osada, J., Browne, J., Loscher, C. E., & Roche, H. M. (2005). Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach. The FASEB Journal, 19(9), 1746-1767. https://doi.org/10.1096/fj.05-3953fje