Effects of 20-week exercise on whole-blood genome-wide DNA methylation profile in children with overweight/obesity

In this project, the effects of a 20-week exercise intervention on whole blood genome-wide DNA methylation signatures (CpG sites level) in boys and girls with overweight/obesity (OW/OB) were investigated. Twenty-three children (10.05 ± 1.39 years, 56% girls) with OW/OB, were randomized to either a 20-week exercise intervention (exercise group [EG]; n=10; 4 boys/ 6 girls), or to usual lifestyle (control group [CG] (n=13; 6 boys/ 7 girls). Whole blood genome-wide DNA methylation and transcriptome profile (RNA-seq) analyses were performed before and after the intervention period. Changes in the DNA methylation sites of 485 and 386 CpGs were induced by the exercise intervention (compared to the control group) in boys and girls respectively (p < 0.001). These CpG sites mapped to loci enriched in distinct gene pathways related to metabolic diseases, fatty acid metabolism, and immune function in boys or girls (p < 0.05). In boys, changes on the DNA methylation status of 87 CpG sites (from the subset of 485 significant CpGs) associated with changes in the gene expression levels of 51 gene transcripts which were regulated by exercise (p < 0.05). Among girls, changes on DNA methylation at 46 CpG sites (from the initial 386 significant CpGs) were associated with changes in the gene expression levels of 30 gene transcripts affected by exercise. Gene transcripts affected by exercise-induced DNA methylation were related to obesity, metabolic syndrome, and inflammation. Nevertheless, none of the presented analyses survived multiple testing correction (FDR > 0.05). This multi-omics approach reveals that exercise may regulate gene pathways involved in metabolism and immune functions in blood cells of boys and girls with OW/OB. These preliminary results provide an important first step to characterize the molecular response to exercise interventions in pediatric populations. Bisulphite converted DNA from the 23 individual in two time points (baseline and t1; 46 samples) were hybridised to the Infinium Methylation EPIC array (Illumina, San Diego, CA, USA).