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Pediatrics

Associations of childhood BMI, general and visceral fat mass with metabolite profiles at school-age

International Journal of Obesity volume 48, pages 1307–1317 (2024)Cite this article

Subjects

Abstract

Background

Childhood obesity increases metabolic disease risk. Underlying mechanisms remain unknown. We examined associations of body mass index (BMI), total body fat mass, and visceral fat mass with serum metabolites at school-age, and explored whether identified metabolites improved the identification of children at risk of a metabolically unhealthy phenotype.

Methods

We performed a cross-sectional analysis among 497 children with a mean age of 9.8 (95% range 9.1, 10.6) years, participating in a population-based cohort study. We measured BMI, total body fat mass using DXA, and visceral fat mass using MRI. Serum concentrations of amino-acids, non-esterified-fatty-acids, phospholipids, and carnitines were determined using LC–MS/MS. Children were categorized as metabolically healthy or metabolically unhealthy, according to BMI, blood pressure, lipids, glucose, and insulin levels.

Results

Higher BMI and total body fat mass were associated with altered concentrations of branched-chain amino-acids, essential amino-acids, and free carnitines. Higher BMI was also associated with higher concentrations of aromatic amino-acids and alkyl-lysophosphatidylcholines (FDR-corrected p-values < 0.05). The strongest associations were present for Lyso.PC.a.C14.0 and SM.a.C32.2 (FDR-corrected p-values < 0.01). Higher visceral fat mass was only associated with higher concentrations of 6 individual metabolites, particularly Lyso.PC.a.C14.0, PC.aa.C32.1, and SM.a.C32.2. We selected 15 metabolites that improved the prediction of a metabolically unhealthy phenotype, compared to BMI only (AUC: BMI: 0.59 [95% CI 0.47,0.71], BMI + Metabolites: 0.91 [95% CI 0.85,0.97]).

Conclusions

An adverse childhood body fat profile, characterized by higher BMI and total body fat mass, is associated with metabolic alterations, particularly in amino acids, phospholipids, and carnitines. Fewer associations were present for visceral fat mass. We identified a metabolite profile that improved the identification of impaired cardiometabolic health in children, compared to BMI only.

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Fig. 1: Associations of childhood BMI and body composition with childhood serum metabolites.
Fig. 2: Receiving operating characteristics (ROC) curves for the prediction of a metabolically healthy or metabolically unhealthy childhood phenotype.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.

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Acknowledgements

We gratefully acknowledge the contribution of participating mothers, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, and the Netherlands Organization for Health Research and Development. RG received funding from the Netherlands Organization for Health Research and Development (NWO, ZonMW 05430052110007; NWO, ZonMw VIDI 09150172110034). VWVJ received a grant from the Netherlands Organization for Health Research and Development (NWO, ZonMw 05430052110007) and a European Research Council Consolidator Grant (ERC-2014-CoG-648916). This project has received funding from the European Union’s Horizon 2020 research and innovation program under the ERA-NET Cofund action (No. 727565), European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL), EndObesity, ZonMW Netherlands (No. 529051026), JPI HDHL BiomarKids, and the German Ministry of Education and Research, Berlin (01EA2101 and 01EA2203A). BK is the Else Kröner Senior Professor of Paediatrics at LMU – University of Munich, financially supported by the charitable Else Kröner-Fresenius-Foundation, LMU Medical Faculty, and LMU University Hospitals.

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Authors and Affiliations

  1. The Generation R Study Group Erasmus MC, University Medical Center, Rotterdam, the Netherlands

    Mireille C. Schipper, Sophia M. Blaauwendraad, Vincent W. V. Jaddoe & Romy Gaillard

  2. Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands

    Mireille C. Schipper, Sophia M. Blaauwendraad, Vincent W. V. Jaddoe & Romy Gaillard

  3. LMU – Ludwig Maximilians Universität Munich, Department of Pediatrics, Dr. von Hauner Children’s Hospital, LMU University Hospitals, Munich, Germany

    Berthold Koletzko

  4. Department of Radiology & Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

    Edwin H. G. Oei

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The author’s responsibilities were as follows. MS, RG, and VJ designed research; MS, RG, and SB conducted research; MS and SB analyzed data; and MS and RG wrote the paper. MS and RG had primary responsibility for the final content. VJ, EO, BK, and SB, critically reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Romy Gaillard.

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Schipper, M.C., Blaauwendraad, S.M., Koletzko, B. et al. Associations of childhood BMI, general and visceral fat mass with metabolite profiles at school-age. Int J Obes 48, 1307–1317 (2024). https://doi.org/10.1038/s41366-024-01558-8

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