Research Article
Sardar Sindhu, Ajit Wilson,
Abstract
Purpose: Toll-like receptors (TLRs) are theinnate immune receptors and some are now found to be involved in metabolic inflammation. TLR4 and TLR2 expressed on cell surface have emerged as immunometabolic receptors, however, the status of endocytic TLRs, especially TLR7 in metabolic disease remains unclear. Therefore, we investigated the adipose tissue expression of TLR7 in obese individuals. Methods: For this purpose, biopsy samples of periumbilical (subcutaneous) fat were collected from 49 individuals classified based on body mass index (BMI) as 22 obese (BMI=34.13±2.81 kg/m2), 18 overweight (BMI=28.26±1.20 kg/m2), and 9 lean (BMI=22.61±2.40 kg/m2) subjects. Expression of the TLR7, TLR-signaling components (MyD88, IRAK1, and TRAF6), macrophage markers (CD68 and CD11c), and inflammatory cytokine (IL-18) was determined by quantitative realtime RT-PCR. Systemic inflammatory marker (C-reactive protein) plasma concentrations were determined by commercial ELISA kit. Data were analyzed using t-test and Pearson’s correlation (r). Results: We found that TLR7 mRNA expression was significantly upregulated in obese (P=0.028) and overweight (P=0.043) as compared with lean individuals; this increase correlated with BMI (r=0.35 P=0.014) and body fat percentage (r=0.39 P=0.007). Moreover, TLR7 gene expression correlated positively/significantly with TLR signaling cascade proteins (MyD88: r=0.39 P=0.005; IRAK1: r=0.38 P=0.008), monocyte/macrophage markers (CD68: r=0.65 P<0.0001; CD11c: r=0.43 P=0.002), and inflammatory signatures (IL-18: r=0.53 P=0.0001; CRP: r=0.44 P=0.008). Conclusion: The upregulated adipose tissue TLR7 expression in obesity is congruent with metabolic inflammatory state and may represent an immune marker in metabolic disease.