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Integrative multi-omics analysis reveals molecular signatures of central obesity in children

Pediatric Research volume 98, pages 1374–1385 (2025)Cite this article

Abstract

Background

Central obesity is associated with an increased risk of hypertension and coronary heart disease. However, its molecular mechanisms have not yet been fully understood. This study aims to investigate lipids and proteins related to childhood central obesity, exploring the molecular mechanisms underlying this condition.

Methods

A case-control study was conducted, including a total of 169 children (aged 7–16 years, 53.25% male, and 74 children in the central obesity group). Plasma lipidomics were measured in all 169 children, and plasma proteomics was measured in 112 of these children. The transcriptomics and lipidomics of the mice’s liver were measured for normal feed and high-fat feed mice.

Results

Forty-six key lipids significantly associated with central obesity were identified, predominantly triglycerides (TAG), with a minority being diacylglycerols (DAG). Additionally, six key proteins, namely PLIN1, PLAT, ADH1A, ADH4, LEP, and INHB, were discovered, which may positively influence the central obesity phenotype by modulating levels of lipids such as TAG, DAG, LDL-C, and HDL-C. These proteins exhibited increased expression in the plasma of children with central obesity. Validation using mouse liver samples showed some overlapping differential lipids between mice and children, albeit minimal overlap in differential genes. This discrepancy may stem from inherent differences between transcriptomics and proteomics, species variations, and differing sampling sites.

Conclusions

PLIN1, PLAT, ADH1A, ADH4, LEP, and INHB are potential significant biomarkers for childhood central obesity and may influence the phenotype of childhood central obesity by modulating levels of lipids such as TAG, DAG, LDL-C, and HDL-C.

Impact

  • PLIN1, PLAT, ADH1A, ADH4, LEP, and INHB are potentially significant biomarkers for childhood central obesity and may influence the phenotype of childhood central obesity by modulating levels of lipids such as TAG, DAG, LDL-C, and HDL-C.

  • Research on integrating lipidomics and proteomics to elucidate the mechanisms of obesity, especially childhood central obesity, remains extremely limited. Our study filled this gap.

  • Our findings highlight potential biomarkers and therapeutic targets that could pave the way for new interventions and treatments to prevent central obesity in children and its harm.

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Fig. 1: The results of the human lipidomic analysis.
Fig. 2: The result of the multivariate logistic regression model of the 46 DELs for central obesity.
Fig. 3: The results of the human proteomic analysis.
Fig. 4: Joint analysis of lipidomics and proteomics.
Fig. 5: The correlation of the 10 proteins with central obesity phenotype.
Fig. 6: Validation by murine data.

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Data availability

Data is available from the corresponding author Xiaohua Liang (Email: xiaohualiang@hospital.cqmu.edu.cn, or liangxiaohua666@sina.com).

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Acknowledgements

The authors would like to acknowledge all the children and the staffs of the six elementary schools in Sichuan and Chongqing.

Funding

This work was supported by the Natural Science Foundation Project (No. 82373590), Joint Medical Research Project of Chongqing Municipal Health Commission and Science and Technology Bureau (2023MSXM036,2025ZDXM008), Program for Youth Innovation in Future Medicine from Chongqing Medical University (No.W0088), General Project of Clinical Medical Research from National Clinical Research Center for Child Health and Disorders (No. NCRCCHD-2022-GP-01), the Young and Middle-aged Medical Outstanding Expert Project of Chongqing Municipal Health Commission (No. 78), Major Health Project of Chongqing Science and Technology Bureau (No. CSTC2021jscx-gksb-N0001, CSTB2023NSCQ-MSX0181), Intelligent Medicine Project (No.ZHYX202109). The funders had no role in the whole study research process, including study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.

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Author notes

  1. These authors contributed equally: Chengzhi Zhao, Xizhou An.

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China

    Chengzhi Zhao, Xizhou An, Leyuan Xiao, Jingyu Chen, Daochao Huang, Lijing Chen & Xiaohua Liang

  2. School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China

    Chengzhi Zhao & Shenying Fang

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  1. Chengzhi Zhao
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Contributions

C.Z.: Methodology, Writing - Review & Editing; F.C., F.C. and L.Y.: Investigation, Supervision; X.Z. and X.C.: Validation, Resources; Q.L. and Q.Z.: Writing – Original Draft, Writing - Review & Editing; X.H.: Conceptualization, Writing - Review & Editing.

Corresponding authors

Correspondence to Shenying Fang or Xiaohua Liang.

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The authors declare no competing interests.

Consent for publication

Approval for this study was obtained from the Institutional Review Board of Chongqing Medical University. Children and their guardians were informed about the details of our research plan. Written informed consent was obtained from each child and their parent or guardian before their inclusion in the study.

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Zhao, C., An, X., Xiao, L. et al. Integrative multi-omics analysis reveals molecular signatures of central obesity in children. Pediatr Res 98, 1374–1385 (2025). https://doi.org/10.1038/s41390-025-03958-6

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