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CC Chemokine and CC Chemokine Receptor Profiles in Visceral and Subcutaneous Adipose Tissue Are Altered in Human Obesity

Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine, III (J.H., F.W.K., M.Z., B.L., T.M.S.), Department of Surgery (G.R.S., G.P.), and Institute of Immunology (G.J.Z.), Medical University of Vienna, 1090 Vienna, Austria

Address all correspondence and requests for reprints to: Thomas M. Stulnig, M.D., Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. E-mail: thomas.stulnig{at}meduniwien.ac.at.

Background/Aims: Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined.

Methods: sc and visceral adipose tissue of obese patients (body mass index 53.1 ± 11.3 kg/m²) compared with lean controls (body mass index 25.9 ± 3.8 kg/m²) was analyzed for alterations in inflammatory gene expression.

Results: Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression.

Conclusion: Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.