TY - JOUR
T1 - Increased adipose tissue expression of IL-18R and its Ligand IL-18 associates with inflammation and insulin resistance in obesity
AU - Ahmad, Rasheed
AU - Thomas, Reeby
AU - Kchumon, Shihab
AU - Sindhu, Sardar
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Adipose tissue
KW - IL-18
KW - IL-18R
KW - Inflammation
KW - Insulin resistance
KW - Obesity
KW - Type-2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85044397242&partnerID=8YFLogxK
U2 - 10.1002/iid3.170
DO - 10.1002/iid3.170
M3 - Article
C2 - 28508444
AN - SCOPUS:85044397242
VL - 5
SP - 318
EP - 335
JO - Immunity, inflammation and disease
JF - Immunity, inflammation and disease
SN - 2050-4527
IS - 3
ER -