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Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants
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Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants
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Journal Article
Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants
2025
Overview
Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications. This high-risk cluster exhibits a complex interplay across many biological pathways, predominantly underscored by inflammation-related cascades. Further, by incorporating comprehensive information from the environmental risk-scape of the critical pregnancy period, we identify pre-pregnancy body mass index and environmental pollutants like perfluorooctanoate and mercury as important determinants of the high-risk cluster. Overall, our work helps to identify potential risk factors for prevention and intervention strategies early in the life course aimed at mitigating obesity and its long-term health consequences.
Obesity encompasses numerous interconnected pathological mechanisms. Here, the authors show that integrating multi-omics data uncovers distinct molecular profiles and prenatal factors linked to childhood obesity and metabolic dysfunction, providing insights for early prevention and intervention strategies.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 49
/ 692/499
/ 692/53
/ Child
/ Children
/ Environmental Pollutants - adverse effects
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mercury
/ Obesity
/ Pediatric Obesity - epidemiology
/ Pediatric Obesity - genetics
/ Pediatric Obesity - metabolism
/ Prenatal Exposure Delayed Effects - genetics
/ Prenatal Exposure Delayed Effects - metabolism
/ Science
