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

INTRODUCTION: The 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. METHODS: We, 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 (mean ± SEM) were analyzed using unpaired t‐test and Pearson's correlation (r); all P values ≤0.05 were considered statistically significant. RESULTS: We 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‐α, 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. CONCLUSIONS: The adipose tissue IL‐18R/IL‐18 expression is enhanced in obesity which associates with proinflammatory gene signature and insulin resistance in these individuals.