Exercise, fitness and health in childhood obesity: a focus on transcriptomics, epigenomics, and proteomics

Résumé

The present Doctoral Thesis examines the relationships of metabolic health, fitness, and exercise with health performing high-throughput omics analyses in blood samples from children with overweight/obesity (OW/OB). Thus, the aims of this Doctoral Thesis were: 1) to examine the differences in the whole-blood transcriptome profiles (RNA-sequencing) of children with metabolic healthy OW/OB compared to metabolic unhealthy OW/OB; 2) to characterize whole-blood transcriptome profile differences between fit and unfit children with OW/OB; 3) to investigate the differences on plasma targeted proteomics between fit and unfit children with OW/OB; 4) To summarize the state-of-the-art of the effect of exercise on gene expression and epigenetic regulation in pediatric population; 5) to study the effects of a 20-week exercise intervention on wholeblood transcriptome profile in children with OW/OB; 6) to report the effects of a 20-week exercise intervention on whole-blood genome-wide DNA methylation profile in children with OW/OB. Six studies were performed within the ActiveBrains project (http://profith.ugr.es/activebrains?lang=en), which were organized into two sections. Section I, Metabolic health and cardiorespiratory fitness levels in children with overweight/obesity: a focus on transcriptomics and proteomics (Studies I, II, and III); and section II: Effects of exercise on transcriptome and epigenome in children with overweight/obesity (Studies IV, V, and VI). The main findings from this thesis were: I) Thirty-two genes were differentially expressed in children with metabolic healthy OW/OB compared to metabolic unhealthy OW/OB, which were mainly related to metabolism, mitochondrial, and immune functions (Study I); II) A different transcriptome profile (256 genes) was identified in fit compared to unfit children with OW/OB, which enriched several molecular pathways related to the immune system and inflammation (Study II); III) 16 proteins involved in neurogenesis, signal transduction, immune function, inflammatory response were differentially expressed in plasma of fit compared to unfit children with OW/OB (Study III); IV) A systematic review was performed, where we gathered the state-of-the-art of the effect of exercise on gene expression and epigenetic regulation, which gathered ten studies that used the candidate gene approach, while two studies performed high-throughput analyses. Most of the studies showed that exercise (acute and chronic effects) alter gene expression, and DNA methylation of candidate genes related to cardiovascular disease, asthma, and immune function (Study IV); V) a 20-week exercise intervention regulated gene pathways involved in immune processes in blood cells in children with OW/OB (Study V); VI) a 20-week exercise intervention demonstrated an impact on DNA methylation profiles of genes involved in metabolic and immune gene pathways. Also, changes of DNA methylation profiles were associated with changes on gene expression levels involved in immune pathways (Study VI). The effects exercise at transcriptomic and epigenomic levels generally did not persist after multiple corrections, so these findings should be considered preliminary and be confirmed in more powerful studies in the future.