Cardiorespiratory fitness in children with overweight/obesity: Insights into the molecular mechanisms
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Aerobic fitnessChildhoodGene expressionRNA-SeqTranscriptome
Plaza-Florido, A... [et al.]. Cardiorespiratory fitness in children with overweight/obesity: Insights into the molecular mechanisms. Scand J Med Sci Sports. 2021; 00: 1– 9. [https://doi.org/10.1111/sms.14028]
SponsorshipSpanish Ministry of Economy and Competitiveness DEP2013-47540 DEP2016-79512-R DEP2017-91544-EXP; Spanish Ministry of Economy, Industry and Competitiveness (MINECO); European Commission RYC-2016-21199; ENDORE SAF2017-87526-R; Junta de Andalucia BIO-302 US-1254251; University of Jaen PAIUJA-EI_CTS02; Spanish Ministry of Education, Culture and Sport FPU 16/02760; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA UO1 TR002004; PERC Systems Biology Fund; Unit of Excellence on EXERNET Research Network on Exercise and Health in Special Populations; Alicia Koplowitz Foundation; Henning Och Johan Throne-Holsts Stiftelse Grant; University of Granada; Unit of Excellence on Exercise and Health (UCEES); Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European Regional; Development Fund (ERDF) SOMM17/6107/UGR European Commission B-CTS-355-UGR18 B-CTS-500-UGR18; Universidad de Granada/CBUA
Objectives: High cardiorespiratory fitness (CRF) levels reduce the risk of developing cardiovascular disease (CVD) during adulthood. However, little is known about the molecular mechanisms underlying the health benefits of high CRF levels at the early stage of life. 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. Design: 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 the limma R/Bioconductor software package (analyses adjusted by sex and maturational status), and pathways’ enrichment analysis was performed with DAVID. In addition, in silico validation data mining was performed using the PHENOPEDIA database. 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 pathway analysis identified gene pathways related to inflammation (eg, dopaminergic and GABAergic synapse pathways). Interestingly, in silico validation data mining detected a set of the differentially expressed genes to be related to CVD, metabolic syndrome, hypertension, inflammation, and asthma. 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.