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Untargeted metabolomics identifies a plasma sphingolipid-related signature associated with lifestyle intervention in prepubertal children with obesity

International Journal of Obesity volume 42, pages 72–78 (2018)Cite this article

Subjects

Abstract

Objective:

Childhood obesity is a strong risk factor for adult obesity and metabolic diseases, including type 2 diabetes and cardiovascular disease. Early lifestyle intervention in children with obesity reduces future disease risk. The objective of this study is to identify metabolic signatures associated with lifestyle intervention in prepubertal children with obesity.

Methods:

Thirty-five prepubertal children (7–10 years) with obesity (body mass index (BMI)>2 standard deviations) were enrolled in the study and participated in a 6-month-long lifestyle intervention program. Physiological and biochemical data and blood samples were collected both at baseline and after the intervention. A liquid chromatography–mass spectrometry (LC–MS)-based metabolomics approach was applied to obtain a comprehensive profiling of plasma samples, identifying 2581 distinct metabolite. Principal component analysis (PCA) was performed to consolidate all features into 8 principal components. Associations between metabolites and physiological and biochemical variables were investigated.

Results:

The intervention program significantly decreased mean (95% CI) BMI standard deviation score from 3.56 (3.29–3.84) to 3.11 (2.88–3.34) (P<0.001). PCA identified one component (PC1) significantly altered by the intervention (Bonferroni adjusted P=0.008). A sphingolipid metabolism-related signature was identified as the major contributor to PC1. Sphingolipid metabolites were decreased by the intervention, and included multiple sphingomyelin, ceramide, glycosylsphingosine and sulfatide species. Changes in several sphingolipid metabolites were associated with intervention-induced improvements in HbA1c levels.

Conclusions:

Decreased circulating sphingolipid-related metabolites were associated with lifestyle intervention in prepubertal children with obesity, and correlated to improvements in HbA1c.

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Acknowledgements

We are very thankful for the families and children that voluntarily participated in the study. We are indebted to the ‘Biobanc de l’Hospital Infantil Sant Joan de Déu per a la Investigació’ integrated in the Spanish Biobank Network of ISCIII for sample processing and procurement. This work was supported by the Seventh Framework Programme Marie Curie FP7-PEOPLE-2011-CIG and the Spanish Government (Ministerio de Economía y Competitividad, RYC2010-06789) to CL.

Author contributions

MJL-W, JCJ-C, MR-K and CL designed the study, analyzed the data and wrote the manuscript; MJL-W, ML and MR-K implemented the intervention and collected data; OY and SS performed the metabolomics analysis; DC performed the statistical analysis; all authors were involved in editing the paper and had final approval of the submitted version. MJL-W, MR-K and CL had full access to the data in the study and final responsibility for the decision to submit for publication.

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Author notes

  1. M J Leal-Witt and M Ramon-Krauel: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, Institut de Recerca Sant Joan de Déu, Barcelona, Spain

    M J Leal-Witt, M Ramon-Krauel, M Llobet, J C Jimenez-Chillaron & C Lerin

  2. Hospital Sant Joan de Déu Barcelona, Barcelona, Spain

    M J Leal-Witt, M Ramon-Krauel, M Llobet, J C Jimenez-Chillaron & C Lerin

  3. Department of Electronic Engineering (DEEEA), Metabolomics Platform, Universitat Rovira i Virgili, Tarragona, Spain

    S Samino & O Yanes

  4. Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain

    S Samino & O Yanes

  5. Department of Statistics, Sant Joan de Déu Research Foundation, Barcelona, Spain

    D Cuadras

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  1. M J Leal-Witt
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Correspondence to C Lerin.

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Leal-Witt, M., Ramon-Krauel, M., Samino, S. et al. Untargeted metabolomics identifies a plasma sphingolipid-related signature associated with lifestyle intervention in prepubertal children with obesity. Int J Obes 42, 72–78 (2018). https://doi.org/10.1038/ijo.2017.201

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