Increased adipose tissue expression of IL-18R and its ligand IL-18 associates with inflammation and insulin resistance in obesity

IntroductionThe proinflammatory cytokine IL-18 is involved in the pathogenesis of metabolic syndrome. While the changes in IL-18 are known, IL-18R expression and relationship with IL-18 and other inflammatory markers in the adipose tissue in obesity/type-2 diabetes (T2D) remain unclear. MethodsWe, therefore, determined the adipose tissue expression of IL-18R and IL-18 mRNA/protein in lean, overweight, and obese individuals with and without T2D, 15 each, using qRT-PCR, immunohistochemistry, and confocal microscopy. Data (meanSEM) were analyzed using unpaired t-test and Pearson's correlation (r); all P values 0.05 were considered statistically significant. ResultsWe found the upregulated gene/protein expression of IL-18R and IL-18 in non-diabetic obese/overweight as compared with lean individuals (P<0.05). BMI correlated positively (P<0.05) with the adipose tissue expression of IL-18R (mRNA: r=0.90 protein: r=0.84) and IL-18 (mRNA: r=0.84 protein: r=0.80). Similarly, in T2D individuals, gene and protein expression of IL-18R/IL-18 was significantly higher in obese as compared with overweight/lean individuals. The BMI was associated with the changes in both IL-18R (mRNA: r=0.55 protein: r=0.50) and IL-18 (mRNA: r=0.53 protein: r=0.57) expression. IL-18R/IL-18 gene expression in the adipose tissue was positively associated (P<0.05) with local gene expression of other inflammatory markers including CD11c, CD86, CD68, CD163, TNF-, and CCL5. Homeostatic model assessment of insulin resistance (HOMA-IR) was higher in diabetic/non-diabetic obese and it correlated with BMI (P<0.05). IL-18R and IL-18 mRNA/protein expression in obesity was associated with HOMA-IR only in non-diabetics. ConclusionsThe adipose tissue IL-18R/IL-18 expression is enhanced in obesity which associates with proinflammatory gene signature and insulin resistance in these individuals.