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

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-01-14 DOI:10.1038/s41467-025-56013-7

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

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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.

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儿童肥胖和代谢功能障碍的多组学架构揭示了生物学途径和产前决定因素

儿童肥胖是一个重大的公共卫生挑战，然而其病理生物学背后的分子复杂性仍然难以捉摸。利用广泛的多组学分析（甲基组、miRNome、转录组、蛋白质和代谢物）和丰富的表型特征，在基于人群的人类早期生活暴露项目中，我们揭示了儿童肥胖和相关代谢功能障碍的分子景观。我们的综合分析揭示了由特定的多组学特征定义的三组儿童，其中一组不仅具有较高的肥胖程度，而且具有高度的代谢并发症。这种高风险集群在许多生物学途径中表现出复杂的相互作用，主要是炎症相关的级联反应。此外，通过综合妊娠关键时期的环境风险情况的综合信息，我们确定孕前体重指数和全氟辛酸盐和汞等环境污染物是高风险群集的重要决定因素。总的来说，我们的工作有助于识别潜在的风险因素，在生命过程的早期预防和干预策略，旨在减轻肥胖及其长期健康后果。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.