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Metabolomic Profiling of Long‐Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain
Author(s) -
Menni Cristina,
Migaud Marie,
Kastenmüller Gabi,
Pallister Tess,
Zierer Jonas,
Peters Annette,
Mohney Robert P.,
Spector Tim D.,
Bagnardi Vincenzo,
Gieger Christian,
Moore Steve C.,
Valdes Ana M.
Publication year - 2017
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21922
Subject(s) - medicine , weight change , body mass index , oxidative stress , weight gain , prostate cancer , gastroenterology , endocrinology , weight loss , obesity , body weight , cancer
Objective To investigate the association between long‐term weight change and blood metabolites. Methods Change in BMI over 8.6 ± 3.79 years was assessed in 3,176 females from the TwinsUK cohort (age range: 18.3‐79.6, baseline BMI: 25.11 ± 4.35) 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). Results Thirty 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 β [95% CI] = 0.05 [0.040 to 0.063]; P = 1.37 × 10 −19 ), gamma‐glutamyl valine (β [95% CI] = 0.06 [0.046 to 0.070]; P = 1.23 × 10 −20 ), butyrylcarnitine (β [95% CI] = 0.04 [0.028 to 0.051]; P = 6.72 × 10 −12 ), and 3‐phenylpropionate (β [95% CI] = −0.03 [−0.041 to −0.019]; P = 9.8 × 10 −8 ), all involved in oxidative stress. Higher levels of urate at baseline were associated with weight gain in KORA and PLCO. Conclusions Metabolites linked to higher oxidative stress are associated with increased long‐term weight gain.