Cardiorespiratory Fitness in Children with Overweight-Obesity: Insights into the Molecular Mechanisms

This study aimed to analyze the whole-blood transcriptome profile of fit children with overweight/obesity (OW/OB) compared to unfit children with OW/OB. Methods: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were evaluated. VO2peak was assessed using a gas analyzer, and participants were categorized into fit or unfit according to the CVD risk-related cut-points. Whole-blood transcriptome profile (RNA sequencing) was analyzed. Differential gene expression analysis was performed using Limma R/Bioconductor software package (analyses adjusted by sex and maturational status). Results: 256 genes were differentially expressed in fit children with OW/OB compared to unfit children with OW/OB after adjusting by sex and maturational status (FDR < 0.05). Enriched pathways analysis identified gene pathways related to inflammation (e.g., dopaminergic and GABAergic synapse pathways). Conclusion: The distinct pattern of whole-blood gene expression in fit children with OW/OB reveals genes and gene pathways that might play a role in reducing CVD risk factors later in life. Total whole blood mRNA profiles of 27 children with overweight/obesity were analyzed by 5’-end RNA sequencing. Cardiorespiratory fitness (i.e., VO2peak) was quantified using a gas analyzer (General Electric Corporation) while performing a maximal incremental treadmill test (HP-Cosmos ergometer). The maturational status of the participants was reflected by peak height velocity (PHV) using age and height in validated algorithms (Moore et al. 2015; PMID: 25423445).