Increased adipose tissue expression of TLR8 in obese individuals with or without type-2 diabetes: Significance in metabolic inflammation

Background: the innate immune toll-like receptors (tlrs) 2/4 are important players in chronic low-grade inflammation called metabolic inflammation in obesity and type-2 diabetes (t2d). while tlr2/4 expression changes associated with metabolic inflammation are known,the adipose tissue expression of endocytic tlr8,which is expressed by all major macrophage subsets,remain unclear. we,therefore,determined the tlr8 mrna/protein expression in the adipose tissue samples from lean,overweight,and obese individuals with or without t2d. methods: subcutaneous fat biopsy samples were collected from 49 non-diabetic (23 obese,17 overweight,and nine lean) and 45 t2d (32 obese,ten overweight,and three lean) individuals. tlr8 gene expression was determined using real-time rt-pcr and tlr8 protein expression was assessed by both immunohistochemistry and confocal microscopy. the changes in tlr8 expression were compared with those of macrophage markers,proinflammatory cytokines/chemokines,and surface tlrs/adapter proteins. the data were analyzed using t-test/mann-whitney u-test,pearson's correlation,and multiple regression test. results: the data show that in obese non-diabetic/t2d individuals,tlr8 gene expression was significantly upregulated as compared with lean individuals which correlated with body mass index (bmi) and body fat percentage in non-diabetic population (p < 0.05). as expected,tlr8 adipose tissue protein expression in non-diabetic/t2d obese individuals was also higher than that of overweight/lean counterparts. in non-diabetic/t2d individuals,tlr8 gene expression associated (p < 0.05) with the expression of cd68,cd11c,cd86,and cd163 macrophage markers. also,in these individuals,tlr8 gene expression correlated positively (p < 0.05) with adipose tissue expression of tnf-α,il-18,and il-8 as well as with systemic crp levels (in non-diabetics). tlr8 expression was also associated with tlr4/tlr2 and myd88 expression in the adipose tissue. conclusions: the elevated adipose tissue expression of tlr8 in obesity/t2d has consensus with inflammatory signatures and may thus represent an immune marker of metabolic inflammation. © 2016 the author(s).