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

Cristina Menni; Marie Migaud; Gabi Kastenmüller; Tess Pallister; Jonas Zierer; Annette Peters; Robert P Mohney; Tim D Spector; Vincenzo Bagnardi; Christian Gieger; Steve C Moore; Ana M Valdes

doi:10.1002/oby.21922

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

Cristina Menni, Marie Migaud, Gabi Kastenmüller, Tess Pallister, Jonas Zierer, Annette Peters, Robert P Mohney, Tim D Spector, Vincenzo Bagnardi, Christian Gieger, Steve C Moore, Ana M Valdes

Twin Research & Genetic Epidemiology

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Abstract

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.

Original language	English
Pages (from-to)	1618-1624
Journal	Obesity
Volume	25
Issue number	9
Early online date	31 Jul 2017
DOIs	https://doi.org/10.1002/oby.21922
Publication status	E-pub ahead of print - 31 Jul 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Menni, C., Migaud, M., Kastenmüller, G., Pallister, T., Zierer, J., Peters, A., Mohney, R. P., Spector, T. D., Bagnardi, V., Gieger, C., Moore, S. C., & Valdes, A. M. (2017). Metabolomic Profiling of Long-Term Weight Change: Role of Oxidative Stress and Urate Levels in Weight Gain. Obesity, 25(9), 1618-1624. Advance online publication. https://doi.org/10.1002/oby.21922

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

abstract = "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.",

keywords = "Journal Article",

author = "Cristina Menni and Marie Migaud and Gabi Kastenm{\"u}ller and Tess Pallister and Jonas Zierer and Annette Peters and Mohney, {Robert P} and Spector, {Tim D} and Vincenzo Bagnardi and Christian Gieger and Moore, {Steve C} and Valdes, {Ana M}",

note = "{\textcopyright} 2017 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).",

year = "2017",

month = jul,

day = "31",

doi = "10.1002/oby.21922",

language = "English",

volume = "25",

pages = "1618--1624",

journal = "Obesity",

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TY - JOUR

T1 - Metabolomic Profiling of Long-Term Weight Change

T2 - Role of Oxidative Stress and Urate Levels in Weight Gain

AU - Menni, Cristina

AU - Migaud, Marie

AU - Kastenmüller, Gabi

AU - Pallister, Tess

AU - Zierer, Jonas

AU - Peters, Annette

AU - Mohney, Robert P

AU - Spector, Tim D

AU - Bagnardi, Vincenzo

AU - Gieger, Christian

AU - Moore, Steve C

AU - Valdes, Ana M

PY - 2017/7/31

Y1 - 2017/7/31

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1002/oby.21922

DO - 10.1002/oby.21922

M3 - Article

C2 - 28758372

SN - 1930-7381

VL - 25

SP - 1618

EP - 1624

JO - Obesity

JF - Obesity

IS - 9

ER -

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

Abstract

Keywords

UN SDGs

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