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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1328.)
© 2009 American Heart Association, Inc.

National Cholesterol Awareness Month

Association of Scavenger Receptors in Adipose Tissue With Insulin Resistance in Nondiabetic Humans

Neda Rasouli; Aiwei Yao-Borengasser; Vijayalakshmi Varma; Horace J. Spencer; Robert E. McGehee, Jr; Charlotte A. Peterson; Jawahar L. Mehta; Philip A. Kern

From the Central Arkansas Veterans Healthcare System (N.R., A.Y.-B., J.L.M.), Division of Endocrinology (N.R., A.Y.-B., V.V.), Division of Cardiovascular Medicine (J.L.M.), Department of Biostatistics (H.J.S.), and the Department of Pediatrics (R.E.M.), University of Arkansas for Medical Sciences; and the Winthrop P. Rockefeller Cancer Institute (R.E.M.), College of Health Sciences (C.A.P.), and the Division of Endocrinology (P.A.K.), University of Kentucky.

Correspondence to Neda Rasouli, MD, Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205. E-mail Rasoulineda{at}uams.edu

Abstract

Objective— Scavenger receptors play crucial roles in the pathogenesis of atherosclerosis, but their role in insulin resistance has not been explored. We hypothesized that scavenger receptors are present in human adipose tissue resident macrophages, and their gene expression is regulated by adiponectin and thaizolidinediones.

Methods and Results— The gene expression of scavenger receptors including scavenger receptor-A (SRA), CD36, and lectin-like oxidized LDL receptor-1 (LOX-1) were studied in subcutaneous adipose tissue of nondiabetic subjects and in vitro. Adipose tissue SRA expression was independently associated with insulin resistance. Pioglitazone downregulated SRA gene expression in adipose tissue of subjects with impaired glucose tolerance and decreased LOX-1 mRNA in vitro. Macrophage LOX-1 expression was decreased when macrophages were cocultured with adipocytes or when exposed to adipocyte conditioned medium. Adding adiponectin neutralizing antibody resulted in a 2-fold increase in LOX-1 gene expression demonstrating that adiponectin regulates LOX-1 expression.

Conclusion— Adipose tissue scavenger receptors are strongly associated with insulin resistance. Pioglitazone and adiponectin regulate gene expression of SRA and LOX-1, and this may have clinical implications in arresting the untoward sequalae of insulin resistance and diabetes, including accelerated atherosclerosis.

The relationship between scavenger receptors and insulin resistance is not well understood. We demonstrated that adipose tissue scavenger receptors are strongly associated with insulin resistance in nondiabetic subjects. Pioglitazone and adiponectin regulated the expression of scavenger receptor A and lectin-like oxidized LDL, and this may have important clinical implications.

Key Words: scavenger receptors • insulin resistance • pioglitazone • adiponectin