Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis

Julia Baumgartl, Stephanie Baudler, Maximilian Scherner, Vladimir Babaev, Liza Makowski, Jill Suttles, Marcia McDuffie, Sergio Fazio, C. Ronald Kahn, Gökhan S. Hotamisligil, Wilhelm Krone, MacRae Linton, Jens C. Brüning

    Research output: Contribution to journalArticle

    92 Scopus citations

    Abstract

    Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1β expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2-/-ApoE-/- cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.

    Original languageEnglish (US)
    Pages (from-to)247-256
    Number of pages10
    JournalCell Metabolism
    Volume3
    Issue number4
    DOIs
    StatePublished - Apr 2006

    ASJC Scopus subject areas

    • Physiology
    • Molecular Biology
    • Cell Biology

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  • Cite this

    Baumgartl, J., Baudler, S., Scherner, M., Babaev, V., Makowski, L., Suttles, J., McDuffie, M., Fazio, S., Kahn, C. R., Hotamisligil, G. S., Krone, W., Linton, M., & Brüning, J. C. (2006). Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis. Cell Metabolism, 3(4), 247-256. https://doi.org/10.1016/j.cmet.2006.02.010