Metabolomics

, Volume 10, Issue 2, pp 259–269 | Cite as

Human metabolic correlates of body mass index

  • Steven C. Moore
  • Charles E. Matthews
  • Joshua N. Sampson
  • Rachael Z. Stolzenberg-Solomon
  • Wei Zheng
  • Qiuyin Cai
  • Yu Ting Tan
  • Wong-Ho Chow
  • Bu-Tian Ji
  • Da Ke Liu
  • Qian Xiao
  • Simina M. Boca
  • Michael F. Leitzmann
  • Gong Yang
  • Yong Bing Xiang
  • Rashmi Sinha
  • Xiao Ou Shu
  • Amanda J. Cross
Original Article

Abstract

A high body mass index (BMI) is a major risk factor for several chronic diseases, but the biology underlying these associations is not well-understood. Dyslipidemia, inflammation, and elevated levels of growth factors and sex steroid hormones explain some of the increased disease risk, but other metabolic factors not yet identified may also play a role. In order to discover novel metabolic biomarkers of BMI, we used non-targeted metabolomics to assay 317 metabolites in blood samples from 947 participants and examined the cross-sectional associations between metabolite levels and BMI. Participants were from three studies in the United States and China. Height, weight, and potential confounders were ascertained by questionnaire (US studies) or direct measurement (Chinese study). Metabolite levels were measured using liquid-phase chromatography and gas chromatography coupled with mass spectrometry. We evaluated study-specific associations using linear regression, adjusted for age, gender, and smoking, and we estimated combined associations using random effects meta-analysis. The meta-analysis revealed 37 metabolites significantly associated with BMI, including 19 lipids, 12 amino acids, and 6 others, at the Bonferroni significance threshold (P < 0.00016). Eighteen of these associations had not been previously reported, including histidine, an amino acid neurotransmitter, and butyrylcarnitine, a lipid marker of whole-body fatty acid oxidation. Heterogeneity by study was minimal (all Pheterogeneity > 0.05). In total, 110 metabolites were associated with BMI at the P < 0.05 level. These findings establish a baseline for the BMI metabolome, and suggest new targets for researchers attempting to clarify mechanistic links between BMI and disease risk.

Keywords

BMI Adiposity Metabolomics Epidemiology Obesity 

Supplementary material

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Copyright information

© Springer Science+Business Media New York (outside the USA)  2013

Authors and Affiliations

  • Steven C. Moore
    • 1
  • Charles E. Matthews
    • 1
  • Joshua N. Sampson
    • 1
  • Rachael Z. Stolzenberg-Solomon
    • 1
  • Wei Zheng
    • 2
  • Qiuyin Cai
    • 2
  • Yu Ting Tan
    • 3
  • Wong-Ho Chow
    • 4
  • Bu-Tian Ji
    • 1
  • Da Ke Liu
    • 3
  • Qian Xiao
    • 1
  • Simina M. Boca
    • 1
  • Michael F. Leitzmann
    • 5
  • Gong Yang
    • 2
  • Yong Bing Xiang
    • 3
  • Rashmi Sinha
    • 1
  • Xiao Ou Shu
    • 2
  • Amanda J. Cross
    • 1
  1. 1.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human ServicesRockvilleUSA
  2. 2.Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Institute for Medicine and Public HealthVanderbilt University School of MedicineNashvilleUSA
  3. 3.Shanghai Cancer InstituteShanghaiChina
  4. 4.University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of Epidemiology and Preventive MedicineRegensburg University Medical CenterRegensburgGermany

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