Objectives: Obesity is associated with low-grade inflammation and insulin resistance that is associated with macrophage infiltration of adipose tissue. The role of chemokines and their receptors in human adipose tissue inflammation remains to be determined.
Methods: Subcutaneous and visceral adipose tissue of obese patients (BMI 53.1±11.3kg/m2) compared to age and sex-matched lean controls (BMI 25.9±3.8kg/m2) was analyzed for the expression of chemokines, chemokine receptors and other inflammatory genes. Blood samples were tested for inflammatory cytokines and markers of insulin resistance.
Results: Macrophage infiltration was increased in subcutaneous and visceral adipose tissue of obese patients as determined by increased mRNA levels of a macrophage-specific marker (CD68). Gene expression of monocyte chemotactic factor-1 (MCP-1, CCL2), monocyte inflammatory protein-1α (MIP-1α, CCL3) and their receptors (CCR1, CCR2 and CCR5) were increased in both subcutaneous and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker interleukin-6 and high sensitive CRP were higher in obese patients compared to lean controls. Obese patients revealed increased insulin resistance as assessed by HOMA index and reduced plasma adiponectin concentrations. Increased adipose tissue chemokine and chemokine receptor expression correlated with BMI and/or insulin resistance.
Conclusion: Upregulation of the chemokines CCL2, CCL3 and their receptors in adipose tissue occurs in human obesity could contribute to the development of obesity-associated adipose tissue inflammation by attracting and activating blood monocytes. A comprehensive analysis of chemokine and chemokine receptor expression in adipose tissue of obese patients is warranted since antagonists of chemokine receptors are potential candidate drugs for diabetes prevention in this population.
This work was supported by the Skoda Award of the Austrian Society for Internal Medicine and the Austrian Science Fund (P18776-B11; both to T.M.S.)
