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Pediatrics

Decreasing severity of obesity from early to late adolescence and young adulthood associates with longitudinal metabolomic changes implicated in lower cardiometabolic disease risk

International Journal of Obesity volume 46, pages 646–654 (2022)Cite this article

Subjects

Abstract

Background

Obesity in childhood is associated with metabolic dysfunction, adverse subclinical cardiovascular phenotypes and adult cardiovascular disease. Longitudinal studies of youth with obesity investigating changes in severity of obesity with metabolomic profiles are sparse. We investigated associations between (i) baseline body mass index (BMI) and follow-up metabolomic profiles; (ii) change in BMI with follow-up metabolomic profiles; and (iii) change in BMI with change in metabolomic profiles (mean interval 5.5 years).

Methods

Participants (n = 98, 52% males) were recruited from the Childhood Overweight Biorepository of Australia study. At baseline and follow-up, BMI and the % >95th BMI-centile (percentage above the age-, and sex-specific 95th BMI-centile) indicate severity of obesity, and nuclear magnetic resonance spectroscopy profiling of 72 metabolites/ratios, log-transformed and scaled to standard deviations (SD), was performed in fasting serum. Fully adjusted linear regression analyses were performed.

Results

Mean (SD) age and % >95th BMI-centile were 10.3 (SD 3.5) years and 134.6% (19.0) at baseline, 15.8 (3.7) years and 130.7% (26.2) at follow-up. Change in BMI over time, but not baseline BMI, was associated with metabolites at follow-up. Each unit (kg/m2) decrease in sex- and age-adjusted BMI was associated with change (SD; 95% CI; p value) in metabolites of: alanine (−0.07; −0.11 to −0.04; p < 0.001), phenylalanine (−0.07; −0.10 to −0.04; p < 0.001), tyrosine (−0.07; −0.10 to −0.04; p < 0.001), glycoprotein acetyls (−0.06; −0.09 to −0.04; p < 0.001), degree of fatty acid unsaturation (0.06; 0.02 to 0.10; p = 0.003), monounsaturated fatty acids (−0.04; −0.07 to −0.01; p = 0.004), ratio of ApoB/ApoA1 (−0.05; −0.07 to −0.02; p = 0.001), VLDL-cholesterol (−0.04; −0.06 to −0.01; p = 0.01), HDL cholesterol (0.05; 0.08 to 0.1; p = 0.01), pyruvate (−0.08; −0.11 to −0.04; p < 0.001), acetoacetate (0.07; 0.02 to 0.11; p = 0.005) and 3-hydroxybuturate (0.07; 0.02 to 0.11; p = 0.01). Results using the % >95th BMI-centile were largely consistent with age- and sex-adjusted BMI measures.

Conclusions

In children and young adults with obesity, decreasing the severity of obesity was associated with changes in metabolomic profiles consistent with lower cardiovascular and metabolic disease risk in adults.

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Fig. 1: Longitudinal associations between lower BMI (per one unit kg/m2) at baseline and metabolite log concentrations (SD units) at follow-up, adjusted for age at each time point and sex.
Fig. 2: Associations between change in BMI (per 1 kg/m2 decrease) between time points and metabolite log concentrations (SD units) at follow-up, adjusted for age at each time point and sex.
Fig. 3: Associations between change in BMI (per 1 kg/m2 decrease) between time points and change in metabolite log concentrations (SD units) between time points, adjusted for age at each time point and sex.

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Code availability

The computer code used in this study is available upon reasonable request, subject to approval by COBRA data custodians.

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Acknowledgements

The authors would like to thank the COBRA participants and their families.

Funding

Research at the Murdoch Children’s Research Institute is supported in part by the Victorian Government Operational Infrastructure Support Program. DB is supported by an NHMRC Investigator Grant (1175744). SB is supported by the Dutch Scientific Organisation (NWO, Rubicon grant no. 452173113).

Author information

Author notes

  1. These authors jointly supervised this work: David Burgner, Christoph Saner.

Authors and Affiliations

  1. Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC, Australia

    Toby Mansell, Joel Nuotio, Tomi T. Laitinen, Brooke E. Harcourt, Siroon Bekkering, Zoe McCallum, Kung-Ting Kao, Matthew A. Sabin, Markus Juonala, Richard Saffery, David Burgner & Christoph Saner

  2. Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia

    Toby Mansell, Brooke E. Harcourt, Zoe McCallum, Kung-Ting Kao, Matthew A. Sabin, Richard Saffery & David Burgner

  3. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

    Costan G. Magnussen, Joel Nuotio & Tomi T. Laitinen

  4. Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland

    Costan G. Magnussen, Joel Nuotio & Tomi T. Laitinen

  5. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia

    Costan G. Magnussen

  6. Heart Centre, Turku University Hospital and University of Turku, Turku, Finland

    Joel Nuotio

  7. Paavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku, Turku, Finland

    Tomi T. Laitinen

  8. Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands

    Siroon Bekkering

  9. Department of Endocrinology, The Royal Children’s Hospital, Parkville, VIC, Australia

    Kung-Ting Kao & Matthew A. Sabin

  10. Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland

    Markus Juonala

  11. Department of Paediatrics, Monash University, Clayton, VIC, Australia

    David Burgner

  12. Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Christoph Saner

  13. Department of Biomedical Research, University of Bern, Bern, Switzerland

    Christoph Saner

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  1. Toby Mansell
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Contributions

TM, DB and CS conceptualised and developed the study. MS set up the cohort, supervised the data collection and critically revised the manuscript. BEH, ZM and K-TK collected data and critically revised the manuscript. TM undertook statistical analysis. CGM assisted with the statistical analysis plan and provided support in interpreting the results. TM, DB and CS drafted the manuscript. JN, TTL, SB, MJ and RS revised the manuscript for important intellectual content. All authors provided expert advice and critical review of the manuscript and approved the final version.

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Correspondence to Christoph Saner.

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Mansell, T., Magnussen, C.G., Nuotio, J. et al. Decreasing severity of obesity from early to late adolescence and young adulthood associates with longitudinal metabolomic changes implicated in lower cardiometabolic disease risk. Int J Obes 46, 646–654 (2022). https://doi.org/10.1038/s41366-021-01034-7

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