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Angiotensin II increases adipose angiotensinogen expression

¹Cardiovascular Research Center, Gill Heart Institute and ²Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky

Submitted 9 June 2006 ; accepted in final form 4 January 2007

In addition to the well-defined contribution of the liver, adipose tissue has been recognized as an important source of angiotensinogen (AGT). The purpose of this study was to define the angiotensin II (ANG II) receptors involved in regulation of adipose AGT and the relationship of this control to systemic AGT and/or angiotensin peptide concentrations. In LDL receptor-deficient (LDLR^–/–) male mice, adipose mRNA abundance of AGT was 68% of that in liver, and adipose mRNA abundance of the angiotensin type 1a (AT_1a) receptor (AT_1aR) was 38% of that in liver, whereas mRNA abundance of the angiotensin type 2 (AT₂) receptor (AT₂R) was 57% greater in adipose tissue than in liver. AGT and angiotensin peptide concentrations were decreased in plasma of AT_1aR-deficient (AT_1aR^–/–) mice and were paralleled by reductions in AGT expression in liver. In contrast, adipose AGT mRNA abundance was unaltered in AT_1aR^–/– mice. AT₂R^–/– mice exhibited elevated plasma angiotensin peptide concentrations and marked elevations in adipose AGT and AT_1aR mRNA abundance. Increases in adipose AGT mRNA abundance in AT₂R^–/– mice were abolished by losartan. In contrast, liver AGT and AT_1aR mRNA abundance were unaltered in AT₂R^–/– mice. Infusion of ANG II for 28 days into LDLR^–/– mice markedly increased adipose AGT and AT_1aR mRNA but did not alter liver AGT and AT_1aR mRNA. These results demonstrate that differential mRNA abundance of AT_1a/AT₂ receptors in adipose tissue vs. liver contributes to tissue-specific ANG II-mediated regulation of AGT. Chronic infusion of ANG II robustly stimulated AT_1aR and AGT mRNA abundance in adipose tissue, suggesting that adipose tissue serves as a primary contributor to the activated systemic renin-angiotensin system.

angiotensin II receptors; renin-angiotensin system; cardiovascular disease; obesity-related disorders; metabolic syndrome

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