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

IL-18R 及其配体 IL-18 的脂肪组织表达增加与肥胖中的炎症和胰岛素抵抗有关

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作者:Rasheed Ahmad, Reeby Thomas, Shihab Kochumon, Sardar Sindhu

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.

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.

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