Journal
OBESITY
Volume 25, Issue 9, Pages 1618-1624Publisher
WILEY
DOI: 10.1002/oby.21922
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Funding
- FP7 project HEALS (Health and Environment-wide Associations based on Large population Surveys) of the European Union's Seventh Framework Programme [603946]
- Medical Research Council Ancestry and Biological Informative Markers for Stratification of Hypertension grant [MR/M016560/1]
- Pfizer
- Wellcome Trust
- European Community's Seventh Framework Programme (FP7)
- National Institute for Health Research (NIHR) Clinical Research Facility at Guy's & St Thomas' National Health Service (NHS) Foundation Trust
- NIHR Biomedical Research Centre, based at Guy's and St Thomas' NHS Foundation Trust
- King's College London
- European Research Council Advanced Principal Investigator award
- NIHR Nottingham Biomedical Research Centre
- Helmholtz Zentrum Munchen German Research Center for Environmental Health
- German Federal Ministry of Education and Research
- State of Bavaria
- Munich Center of Health Sciences, Ludwing-Maximilians-Universitat, as part of LMUinnovativ
- Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services
- Breast Cancer Research Stamp Fund
- British Heart Foundation [SP/14/8/31352] Funding Source: researchfish
- Medical Research Council [MR/M016560/1] Funding Source: researchfish
- MRC [MR/M016560/1] Funding Source: UKRI
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ObjectiveTo investigate the association between long-term weight change and blood metabolites. MethodsChange in BMI over 8.63.79 years was assessed in 3,176 females from the TwinsUK cohort (age range: 18.3-79.6, baseline BMI: 25.114.35) measured for 280 metabolites at follow-up. Statistically significant metabolites (adjusting for covariates) were included in a multivariable least absolute shrinkage and selection operator (LASSO) model. Findings were replicated in the Cooperative Health Research in the Region of Augsburg (KORA) study (n=1,760; age range: 25-70, baseline BMI: 27.72 +/- 4.53). The study examined whether the metabolites identified could prospectively predict weight change in KORA and in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) study (n=471; age range: 55-74, baseline BMI:27.24 +/- 5.37). ResultsThirty metabolites were significantly associated with change in BMI per year in TwinsUK using Bonferroni correction. Four were independently associated with weight change in the multivariable LASSO model and replicated in KORA: namely, urate (meta-analysis [95% CI]=0.05 [0.040 to 0.063]; P=1.37x10(-19)), gamma-glutamyl valine ( [95% CI]=0.06 [0.046 to 0.070]; P=1.23x10(-20)), butyrylcarnitine ( [95% CI]=0.04 [0.028 to 0.051]; P=6.72x10(-12)), and 3-phenylpropionate ( [95% CI]=-0.03 [-0.041 to -0.019]; P=9.8x10(-8)), all involved in oxidative stress. Higher levels of urate at baseline were associated with weight gain in KORA and PLCO. ConclusionsMetabolites linked to higher oxidative stress are associated with increased long-term weight gain.
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