Angiotensin type 1 receptor modulates macrophage polarization and renal injury in obesity

Li Jun Ma, Bridgette A. Corsa, Jun Zhou, Haichun Yang, Haijing Li, Yi Wei Tang, Vladimir R. Babaev, Amy S. Major, Macrae F. Linton, Sergio Fazio, Tracy E. Hunley, Valentina Kon, Agnes B. Fogo

    Research output: Contribution to journalArticle

    64 Scopus citations

    Abstract

    The mechanisms for increased risk of chronic kidney disease (CKD) in obesity remain unclear. The renin-angiotensin system is implicated in the pathogenesis of both adiposity and CKD. We investigated whether the angiotensin type 1 (AT1) receptor, composed of dominant AT1a and less expressed AT1b in wild-type (WT) mice, modulates development and progression of kidney injury in a high-fat diet (HFD)-induced obesity model. WT mice had increased body weight, body fat, and insulin levels and decreased adiponectin levels after 24 wk of a high-fat diet. Identically fed AT1a knockout (AT1aKO) mice gained weight similarly to WT mice, but had lower body fat and higher plasma cholesterol. Both obese AT1aKO and obese WT mice had increased visceral fat and kidney macrophage infiltration, with more proinflammatory M1 macrophage markers as well as increased mesangial expansion and tubular vacuolization, compared with lean mice. These abnormalities were heightened in the obese AT1aKO mice, with downregulated M2 macrophage markers and increased macrophage AT1b receptor. Treatment with an AT1 receptor blocker, which affects both AT1a and AT1b, abolished renal macrophage infiltration with inhibition of renal M1 and upregulation of M2 macrophage markers in obese WT mice. Our data suggest obesity accelerates kidney injury, linked to augmented inflammation in adipose and kidney tissues and a proinflammatory shift in macrophage and M1/M2 balance.

    Original languageEnglish (US)
    Pages (from-to)1203-1213
    Number of pages11
    JournalAmerican Journal of Physiology - Renal Physiology
    Volume300
    Issue number5
    DOIs
    StatePublished - May 1 2011

    Keywords

    • Chronic kidney disease
    • Inflammation

    ASJC Scopus subject areas

    • Physiology
    • Urology

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  • Cite this

    Ma, L. J., Corsa, B. A., Zhou, J., Yang, H., Li, H., Tang, Y. W., Babaev, V. R., Major, A. S., Linton, M. F., Fazio, S., Hunley, T. E., Kon, V., & Fogo, A. B. (2011). Angiotensin type 1 receptor modulates macrophage polarization and renal injury in obesity. American Journal of Physiology - Renal Physiology, 300(5), 1203-1213. https://doi.org/10.1152/ajprenal.00468.2010