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Angiotensin II Regulates Adipocyte Apolipoprotein E Expression

Departments of Medicine (P.R., Z.H.H., T.M.) and Pharmacology (T.M.), University of Illinois at Chicago, Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Theodore Mazzone, M.D., Section of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, 1819 West Polk Street (MC 797), Chicago, Illinois 60612. 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 apolipoprotein E (apoE) in adipose tissue has been shown to have important effects on adipocyte lipid flux and gene expression. Adipose tissue is also a physiological target of angiotensin II (AII).

Objective: The aim of the current study was to evaluate a potential regulatory effect for AII on adipose tissue apoE expression.

Results: Infusion of AII into mice for 3 d significantly reduced apoE expression in adipocytes from freshly isolated adipose tissue. ApoE expression was unchanged by the AII infusion in the stromovascular fraction. In isolated human adipocytes, treatment with AII significantly reduced cellular and secreted apoprotein E (by 20–60%). Suppression of apoE expression was observed in sc adipocytes obtained from nonobese (body mass index < 30 kg/m²) donors, and in sc and omental adipocytes obtained from obese (body mass index > 30 kg/m²) donors. Evaluation of the effect of AII in matched sets of sc 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 sc and omental adipocytes from all three subjects. The specific AT₁ receptor blocker, valsartan, eliminated the effect of AII 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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