Increased expression of IRF-5 in the adipose tissue in obesity: Implication in metabolic inflammation

Abstract

Abstract Obesity is marked by a state of chronic low-grade inflammation called metabolic inflammation which plays a role in the development of insulin resistance and type-2 diabetes (T2D). We and others have shown that the innate immune toll-like receptors (TLRs) are involved in metabolic inflammation/insulin resistance. The transcription factor called interferon regulatory factor (IRF)-5 is a major regulator of proinflammatory macrophage polarization; however, its role in obesity/T2D remains unclear. Therefore, we determined modulations in the IRF-5 expression and analyzed their relationship with signature metabolic inflammatory markers in the subcutaneous adipose tissues (AT) obtained from adult persons classified as lean, overweight, and obese on the basis of BMI. The data show that IRF-5 expression was upregulated (P<0.05) in obese as compared with lean individuals at both mRNA and protein levels; and these changes correlated with BMI (r=0.3; P= 0.03) and body fat percentage (r=0.48; P=0.0005). The elevated IRF-5 expression also correlated positively (P<0.05) with various inflammatory markers including TNF-α (r=0.47), IL-6 (r=0.31), IL-1β (0.36), IL-18 (r=0.27), CXCL-10 (r=0.30); IL-8 (r= 0.33), CCL-5 (r=0.41); CCR-5 (r=0.42); CCR-2 (0.54) as well as TLR adapter proteins MyD88 (r=0.61) and IRAK-1 (r=0.50). Interestingly, IRF-5 expression was found to associate with fasting blood glucose (r=0.40, P = 0.008) and glycated hemoglobin (r=0.45, P=0.009). As expected, IRF-5 expression correlated negatively with plasma adiponectin levels (r= −0.43; P=0.009). Collectively, our data show that increased AT- IRF-5 expression is concordant with signature inflammatory markers which may have significance in metabolic inflammation.