Metabolomic Profiling of Long-Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain

被引:25
|
作者
Menni, Cristina [1 ]
Migaud, Marie [2 ]
Kastenmueller, Gabi [1 ,3 ,4 ]
Pallister, Tess [1 ]
Zierer, Jonas [1 ,3 ]
Peters, Annette [5 ]
Mohney, Robert P. [6 ]
Spector, Tim D. [1 ]
Bagnardi, Vincenzo [7 ]
Gieger, Christian [5 ]
Moore, Steve C. [8 ]
Valdes, Ana M. [1 ,9 ,10 ]
机构
[1] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
[2] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA
[3] Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany
[4] German Ctr Diabet Res, Neuherberg, Germany
[5] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany
[6] Metabolon Inc, Durham, NC USA
[7] Univ Milano Bicocca, Dept Stat & Quantitat Methods, Milan, Italy
[8] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA
[9] Univ Nottingham, Sch Med, Nottingham, England
[10] Nottingham Biomed Res Ctr, Natl Inst Hlth Res, Nottingham, England
基金
英国惠康基金; 欧洲研究理事会; 美国国家卫生研究院; 英国医学研究理事会;
关键词
INSULIN-RESISTANCE; URIC-ACID; SKELETAL-MUSCLE; REDOX STATE; OBESITY; POPULATION; RISK; ACYLCARNITINES; ANTIOXIDANTS; BIOMARKERS;
D O I
10.1002/oby.21922
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1618 / 1624
页数:7
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