Metabolomic Signatures of Habitual Physical Activity in Childhood
Abstract
Physical activity (PA) supports health across the life course, yet the biological pathways linking habitual PA to long-term health remain incompletely understood. Metabolomics provides a powerful tool to study PA-related metabolic adaptations, but how habitual PA shapes the metabolome in childhood remains poorly characterized. Addressing this gap, we examined cross-sectional associations between accelerometer-measured habitual PA and the plasma metabolome in 515 children aged 5.5 to 11 years from the European Childhood Obesity Project (CHOP) and additionally determined whether associations differed between sexes and across the body mass index (BMI) range. Using targeted metabolomics, we quantified 315 metabolites and derived 91 metabolite sums and ratios. Associations with PA were assessed using linear mixed-effects models. Replication was performed in an independent pediatric cohort. Among the 406 metabolite variables, 73 were associated (p < 0.05) with at least one PA variable, of which 12 replicated, including lysophosphatidylcholine (LPC) a C14:0 and LPCs/phosphatidylcholines (PCs) with higher levels in more active children, and PC aa C40:6, monounsaturated PCs/saturated PCs, and valine/LPC a C18:1 with lower levels in more active children. At the metabolite-class level, intensity-dependent association patterns emerged. Amino acids and acylcarnitines were lower in more active children predominantly for time spent in higher-intensity PA, whereas LPCs were higher mainly with more total PA (80% light PA) and less sedentary time. Associations were more pronounced at older ages and differed (p < 0.05) by BMI for 42 metabolite variables and by sex for 45 variables in the interaction analyses. These findings provide insights into PA-related metabolic adaptations early in life and may help elucidate biological pathways linking childhood PA to long-term health.
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BibTeX
@misc{vehovec2026metabolomic,
title = {{Metabolomic Signatures of Habitual Physical Activity in Childhood}},
author = {Lara Vehovec and Jill Fründ and Jeannie Horak and Kathrin Guerlich and Hans Demmelmair and Mireia Alcázar and Werner Römisch-Margl and Fabian Geyer and Elvira Verduci and Dariusz Gruszfeld and Annick Xhonneux and Joaquín Escribano and Berthold Koletzko and Veronica Luque and Veit Grote and Gabi Kastenmüller},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.26366930},
url = {https://www.medrxiv.org/content/10.64898/2026.10.30.26366930v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Metabolomic Signatures of Habitual Physical Activity in Childhood
AU - Lara Vehovec
AU - Jill Fründ
AU - Jeannie Horak
AU - Kathrin Guerlich
AU - Hans Demmelmair
AU - Mireia Alcázar
AU - Werner Römisch-Margl
AU - Fabian Geyer
AU - Elvira Verduci
AU - Dariusz Gruszfeld
AU - Annick Xhonneux
AU - Joaquín Escribano
AU - Berthold Koletzko
AU - Veronica Luque
AU - Veit Grote
AU - Gabi Kastenmüller
PY - 2026
DA - 2026/10/30
PB - medRxiv
DO - 10.64898/2026.10.30.26366930
UR - https://www.medrxiv.org/content/10.64898/2026.10.30.26366930v1
AB - Physical activity (PA) supports health across the life course, yet the biological pathways linking habitual PA to long-term health remain incompletely understood. Metabolomics provides a powerful tool to study PA-related metabolic adaptations, but how habitual PA shapes the metabolome in childhood remains poorly characterized. Addressing this gap, we examined cross-sectional associations between accelerometer-measured habitual PA and the plasma metabolome in 515 children aged 5.5 to 11 years from the European Childhood Obesity Project (CHOP) and additionally determined whether associations differed between sexes and across the body mass index (BMI) range. Using targeted metabolomics, we quantified 315 metabolites and derived 91 metabolite sums and ratios. Associations with PA were assessed using linear mixed-effects models. Replication was performed in an independent pediatric cohort. Among the 406 metabolite variables, 73 were associated (p < 0.05) with at least one PA variable, of which 12 replicated, including lysophosphatidylcholine (LPC) a C14:0 and LPCs/phosphatidylcholines (PCs) with higher levels in more active children, and PC aa C40:6, monounsaturated PCs/saturated PCs, and valine/LPC a C18:1 with lower levels in more active children. At the metabolite-class level, intensity-dependent association patterns emerged. Amino acids and acylcarnitines were lower in more active children predominantly for time spent in higher-intensity PA, whereas LPCs were higher mainly with more total PA (80% light PA) and less sedentary time. Associations were more pronounced at older ages and differed (p < 0.05) by BMI for 42 metabolite variables and by sex for 45 variables in the interaction analyses. These findings provide insights into PA-related metabolic adaptations early in life and may help elucidate biological pathways linking childhood PA to long-term health.
ER -