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
Institute for Global Health (ISGlobal), Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Nat Commun. 2025 Jan 14;16(1):654. doi: 10.1038/s41467-025-56013-7.
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.
儿童肥胖对公共卫生构成了重大挑战，但其病理生物学背后的分子复杂性仍然难以捉摸。在基于人群的人类早期生活暴露组项目中，利用欧洲两个地区广泛的多组学分析（甲基化组、微小RNA组、转录组、蛋白质组和代谢组）以及丰富的表型特征，我们揭示了儿童肥胖和相关代谢功能障碍的分子图景。我们的综合分析发现了由特定多组学特征定义的三组儿童，其中一组不仅以更高的肥胖程度为特征，还伴有高度的代谢并发症。这个高风险组在许多生物途径中表现出复杂的相互作用，主要由炎症相关级联反应突出显示。此外，通过纳入关键孕期环境风险状况的全面信息，我们确定孕前体重指数以及全氟辛酸和汞等环境污染物是高风险组的重要决定因素。总体而言，我们的工作有助于识别生命早期预防和干预策略的潜在风险因素，旨在减轻肥胖及其长期健康后果。
