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

Ma LJ, Corsa BA, Zhou J, Yang H, Li H, Tang YW, Babaev VR, Major AS, Linton MF, Fazio S, Hunley TE, Kon V, Fogo AB
Am J Physiol Renal Physiol. 2011 300 (5): F1203-13

PMID: 21367915 · PMCID: PMC3094053 · DOI:10.1152/ajprenal.00468.2010

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 (AT(1)) receptor, composed of dominant AT(1a) and less expressed AT(1b) 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 AT(1a) 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 AT(1b) receptor. Treatment with an AT(1) receptor blocker, which affects both AT(1a) and AT(1b), 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.

MeSH Terms (22)

Adiponectin Adiposity Angiotensin II Type 1 Receptor Blockers Animals Biomarkers Body Weight Cholesterol Dietary Fats Disease Models, Animal Hemodynamics Inflammation Mediators Insulin Intra-Abdominal Fat Kidney Kidney Diseases Macrophages Male Mice Mice, Inbred C57BL Mice, Knockout Obesity Receptor, Angiotensin, Type 1

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