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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2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56013-7 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nikos Stratakis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-764727d0a085444b98d1be3d60e07c00 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-764727d0a085444b98d1be3d60e07c002025-01-19T12:30:14ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-56013-7Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinantsNikos Stratakis0Augusto Anguita-Ruiz1Lorenzo Fabbri2Léa Maitre3Juan R. González4Sandra Andrusaityte5Xavier Basagaña6Eva Borràs7Hector C. Keun8Lida Chatzi9David V. Conti10Jesse Goodrich11Regina Grazuleviciene12Line Småstuen Haug13Barbara Heude14Wen Lun Yuan15Rosemary McEachan16Mark Nieuwenhuijsen17Eduard Sabidó18Rémy Slama19Cathrine Thomsen20Jose Urquiza21Theano Roumeliotaki22Marina Vafeiadi23John Wright24Mariona Bustamante25Martine Vrijheid26Institute for Global Health (ISGlobal)Institute for Global Health (ISGlobal)Institute for Global Health (ISGlobal)Institute for Global Health (ISGlobal)Institute for Global Health (ISGlobal)Department of Environmental Sciences, Vytautas Magnus UniversityInstitute for Global Health (ISGlobal)Universitat Pompeu Fabra (UPF)Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College LondonDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern CaliforniaDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern CaliforniaDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern CaliforniaDepartment of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Institute of Biomedicine of the University of Barcelona (IBUB), Universitat de Barcelona (UB)Department of Food Safety, Norwegian Institute of Public HealthUniversité Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS)Université Paris Cité and Université Sorbonne Paris Nord, Inserm, INRAE, Center for Research in Epidemiology and StatisticS (CRESS)Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation TrustInstitute for Global Health (ISGlobal)Universitat Pompeu Fabra (UPF)Department of Prevention and Treatment of Chronic Diseases, Institute for Advanced Biosciences (IAB), INSERM U1209, CNRS UMR 5309, Université Grenoble AlpesDepartment of Food Safety, Norwegian Institute of Public HealthInstitute for Global Health (ISGlobal)Department of Social Medicine, University of CreteDepartment of Social Medicine, University of CreteBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation TrustInstitute for Global Health (ISGlobal)Institute for Global Health (ISGlobal)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.https://doi.org/10.1038/s41467-025-56013-7 |
| spellingShingle | 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 Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants Nature Communications |
| title | Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants |
| title_full | Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants |
| title_fullStr | Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants |
| title_full_unstemmed | Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants |
| title_short | Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants |
| title_sort | multi omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants |
| url | https://doi.org/10.1038/s41467-025-56013-7 |
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