Institute of Food Sciences, National Research Council, 83100 Avellino, Italy.
Leibniz Institute for Prevention Research and Epidemiology-BIPS, Achterstraße 30, 28359 Bremen, Germany.
Genes (Basel). 2022 Apr 1;13(4):632. doi: 10.3390/genes13040632.
Increasing data suggest that overnutrition-induced obesity may trigger an inflammatory process in adipose tissue and upturn in the innate immune system. Numerous players have been involved 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 candidate miRNAs in relation to inflammation-associated biomarkers in a subsample of European children with overweight and obesity participating in the I.Family study. The study sample included individuals with increased adiposity since this condition contributes to the early occurrence of chronic low-grade inflammation. We focused on the acute-phase reagent C-reactive protein (CRP) as the primary outcome and selected cytokines as plausible biomarkers of inflammation. We found that chronic low-grade CRP elevation shows a highly significant association with miR-26b-3p and hsa-miR-576-5p in boys. Furthermore, the association of CRP with hsa-miR-10b-5p and hsa-miR-31-5p is highly significant in girls. We also observed major sex-related associations of candidate miRNAs with selected cytokines. Except for IL-6, a significant association of hsa-miR-26b-3p and hsa-miR-576-5p with TNF-α, IL1-Ra, IL-8, and IL-15 levels was found exclusively in boys. The findings of this exploratory study suggest sex differences in the association of circulating miRNAs with inflammatory response biomarkers, and indicate a possible role of miRNAs among the candidate epigenetic mechanisms related to the process of low-grade inflammation in childhood obesity.
越来越多的证据表明，营养过剩引起的肥胖可能会在脂肪组织中引发炎症过程，并导致先天免疫系统失衡。许多因素参与了炎症反应的调控，包括表观遗传学。在表观遗传学因素中，miRNA 作为免疫细胞发育、免疫反应、自身免疫和炎症的关键调节因子而崭露头角。在这项研究中，我们旨在确定候选 miRNA 是否与超重和肥胖的欧洲儿童亚组的炎症相关生物标志物有关，这些儿童参与了 I.Family 研究。研究样本包括因肥胖而出现的个体，因为这种情况会导致慢性低度炎症的早期发生。我们专注于急性期反应物 C 反应蛋白（CRP）作为主要结果，并选择细胞因子作为炎症的可能生物标志物。我们发现，慢性低度 CRP 升高与男孩的 miR-26b-3p 和 hsa-miR-576-5p 高度相关。此外，CRP 与 hsa-miR-10b-5p 和 hsa-miR-31-5p 在女孩中的关联也具有高度显著性。我们还观察到候选 miRNA 与选定细胞因子之间存在主要的性别相关关联。除了 IL-6，我们还发现 hsa-miR-26b-3p 和 hsa-miR-576-5p 与 TNF-α、IL1-Ra、IL-8 和 IL-15 水平之间的显著关联仅存在于男孩中。这项探索性研究的结果表明，循环 miRNA 与炎症反应生物标志物的关联存在性别差异，并表明 miRNA 可能在与儿童肥胖低度炎症过程相关的候选表观遗传机制中发挥作用。
