Integrated Analysis of Methylome and Transcriptome Responses to Exercise Training in Children with Overweight/Obesity.

We examined the effects of a 20-week exercise intervention on whole-blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). 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 methylome (CpG sites) analysis using Infinium Methylation EPIC array and transcriptome analysis using RNA-seq (STRT2 protocol) were performed. Exercise induced modifications in DNA methylation at 485 and 386 CpGs sites in boys and girls respectively. These CpG sites mapped to loci enriched in distinct gene pathways related to metabolic diseases, fatty acid metabolism, and immune function. In boys, changes in the DNA methylation of 87 CpG sites (18% of the 485 CpGs sites altered by exercise) were associated with changes in the gene expression levels of 51 genes also regulated by exercise. Among girls, changes in DNA methylation at 46 CpG sites (12% of the initial 386 significant CpGs) were associated with changes in the expression levels of 30 exercise-affected genes. Genes affected by exercise that were associated with DNA methylation are related to obesity, metabolic syndrome, and inflammation. Multi-omics analysis of whole-blood samples from children with OW/OB, suggests that gene expression response to exercise may be modulated by DNA methylation and involve gene pathways related to metabolism and immune functions.