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

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

Abstract 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...

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Main Authors: Nikos Stratakis, Augusto Anguita-Ruiz, Lorenzo Fabbri, Léa Maitre, Juan R. González, Sandra Andrusaityte, Xavier Basagaña, Eva Borràs, Hector C. Keun, Lida Chatzi, David V. Conti, Jesse Goodrich, Regina Grazuleviciene, Line Småstuen Haug, Barbara Heude, Wen Lun Yuan, Rosemary McEachan, Mark Nieuwenhuijsen, Eduard Sabidó, Rémy Slama, Cathrine Thomsen, Jose Urquiza, Theano Roumeliotaki, Marina Vafeiadi, John Wright, Mariona Bustamante, Martine Vrijheid
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56013-7
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Summary:Abstract 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.
ISSN:2041-1723

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