Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants

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...

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Veröffentlicht in:Nature communications Jg. 16; H. 1; S. 654 - 15
Hauptverfasser: Stratakis, Nikos, Anguita-Ruiz, Augusto, Fabbri, Lorenzo, Maitre, Léa, González, Juan R., Andrusaityte, Sandra, Basagaña, Xavier, Borràs, Eva, Keun, Hector C., Chatzi, Lida, Conti, David V., Goodrich, Jesse, Grazuleviciene, Regina, Haug, Line Småstuen, Heude, Barbara, Yuan, Wen Lun, McEachan, Rosemary, Nieuwenhuijsen, Mark, Sabidó, Eduard, Slama, Rémy, Thomsen, Cathrine, Urquiza, Jose, Roumeliotaki, Theano, Vafeiadi, Marina, Wright, John, Bustamante, Mariona, Vrijheid, Martine
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 14.01.2025
Nature Publishing Group
Nature Portfolio
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Adipose tissue
Adiposity
Biological analysis
Body Mass Index
Body size
Child
Child, Preschool
Childhood
Children
Cluster analysis
Environmental Pollutants - adverse effects
Environmental risk
Europe - epidemiology
Female
Humanities and Social Sciences
Humans
Male
Mercury
Metabolism
Metabolites
multidisciplinary
Multiomics
Obesity
Pediatric Obesity - epidemiology
Pediatric Obesity - genetics
Pediatric Obesity - metabolism
Pollution index
Pregnancy
Prenatal Exposure Delayed Effects - genetics
Prenatal Exposure Delayed Effects - metabolism
Prevention
Public health
Risk Factors
Science
Science (multidisciplinary)
Transcriptome
Transcriptomes
Europe
ISSN:2041-1723, 2041-1723
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Zusammenfassung: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.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-025-56013-7