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Submitted on July 17, 2007
Accepted on August 29, 2007
Department of Medicine, University of Illinois at Chicago; Departments of Medicine and Pharmacology, University of Illinois at Chicago, Chicago, Illinois
* To whom correspondence should be addressed. E-mail: tmazzone{at}uic.edu.
Context: Obesity is increasing in prevalence and it is important to understand factors that regulate adipose tissue lipid metabolism. Recently, endogenous expression of apoE in adipose tissue has been shown to have important effects on adipocyte lipid flux and gene expression. Adipose tissue is also a physiologic target of angiotensin II.
Objective: The aim of the current study was to evaluate a potential regulatory effect for angiotensin II on adipose tissue apoE expression.
Results: Infusion of angiotensin II into mice for 3 days significantly reduced apoE expression in adipocytes from freshly isolated adipose tissue. ApoE expression was unchanged by the angiotensin II infusion in the stromovascular fraction. In isolated human adipocytes, treatment with angiotensin II significantly reduced cellular and secreted apoprotein E (by 20–60%). Suppression of apoE expression was observed in subcutaneous adipocytes obtained from non-obese (body mass index <30 kg/m2) donors, and in subcutaneous and omental adipocytes obtained from obese (body mass index >30 kg/m2) donors. Evaluation of the effect of angiotensin II in matched sets of subcutaneous and omental adipocytes from three separate donors showed lower overall apoE expression in omental adipocytes in two of the donors, and a concordant down-regulation of apoE expression in subcutaneous and omental adipocytes from all three subjects. The specific AT1 receptor blocker, valsartan, eliminated the effect of angiotensin II on adipocyte apoE expression.
Conclusion: Both apoE and components of the renin-angiotensin system are expressed in adipose tissue, and each has important effects on adipocyte lipid metabolism and gene expression. The regulatory interaction we have identified between these two pathways has important implications for a complete understanding of adipose tissue lipid homeostasis.
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