Plasma microRNA expression profiles are associated with early childhood obesity: results of the I.Family Study

Background: Nearly ten years ago, the WHO reported the increasing prevalence of obesity worldwide as a challenge for public health due the associated adverse consequences. Omic studies demonstrated that microRNA (miRNA) changes in tissues correlate with several diseases, including obesity. Other studies suggested a remarkable stability of miRNA also in blood, emphasing their potential as theranostic agents. Aim: This study investigated the profiles of circulating miRNAs in plasma samples of normal weight (n=159) and overweight/obese (n=149) children participating to the I.Family study, an EC funded study finalized to investigate the etiology of overweight, obesity and related disorders in children of eight European countries (www.ifamilystudy.eu). Differences in miRNA expression patterns with respect to anthropometric and biochemical variables were explored. Results: A high degree of variability in levels of circulating miRNAs was recognised among children from different countries. Several miRNAs differentially expressed in overweight/low grade obesity children were characterized (miR-551a and miR-501-5p up-regulated; miR-10b-5p, miR-191-3p, miR-215-5p and miR-874-3p down-regulated). ROC curves were constructed for confirmed miRNAs. Single miRNAs exhibited low AUC values with the highest values for miR-874-3p and miR-501-5p which in combination provided an interesting value (AUC=0.755). Pearson's analysis confirmed that miR-10b-5p, miR-215-5p, miR-501-5p, miR-551a, and miR-874-3p correlated with BMI z-score. Molecular interactions of obesity-associated miRNAs were also predicted. Computational analysis indicated that miRNAs act as key regulators of metabolism, playing pivotal roles in early stages of obesity by affecting multiple candidate genes. Conclusions: Although causal pathways cannot be definitely inferred it is conceivable that circulating miRNAs may be new biomarkers of early childhood obesity.