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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Vydáno v:	Nature communications Ročník 16; číslo 1; s. 654 - 15
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 14.01.2025 Nature Publishing Group Nature Portfolio
Témata:	38 49 692/163/2743/393 692/499 692/53 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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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-025-56013-7