Circulating miRNAs Are Associated with Inflammation Biomarkers in Children with Overweight and Obesity: Results of the I.Family Study

Increasing data suggest that overnutrition-induced obesity may trigger an inflammatoryprocess in adipose tissue and upturn in the innate immune system. Numerous players have beeninvolved in governing the inflammatory response, including epigenetics. Among epigenetic players,miRNAs are emerging as crucial regulators of immune cell development, immune responses, autoimmunity,and inflammation. In this study, we aimed at identifying the involvement of candidatemiRNAs in relation to inflammation-associated biomarkers in a subsample of European children withoverweight and obesity participating in the I.Family study. The study sample included individualswith increased adiposity since this condition contributes to the early occurrence of chronic low-gradeinflammation. We focused on the acute-phase reagent C-reactive protein (CRP) as the primaryoutcome and selected cytokines as plausible biomarkers of inflammation. We found that chroniclow-grade CRP elevation shows a highly significant association with miR-26b-3p and hsa-miR-576-5pin boys. Furthermore, the association of CRP with hsa-miR-10b-5p and hsa-miR-31-5p is highly significantin girls. We also observed major sex-related associations of candidate miRNAs with selectedcytokines. Except for IL-6, a significant association of hsa-miR-26b-3p and hsa-miR-576-5p withTNF-, IL1-Ra, IL-8, and IL-15 levels was found exclusively in boys. The findings of this exploratorystudy suggest sex differences in the association of circulating miRNAs with inflammatory responsebiomarkers, and indicate a possible role of miRNAs among the candidate epigenetic mechanismsrelated to the process of low-grade inflammation in childhood obesity.