Human metabolic correlates of body mass index - PubMed (original) (raw)

. 2014 Apr 1;10(2):259-269.

doi: 10.1007/s11306-013-0574-1.

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

Affiliations

Human metabolic correlates of body mass index

Steven C Moore et al. Metabolomics. 2014.

Abstract

Background: 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.

Design: 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.

Results: 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.

Conclusion: These findings establish a baseline for the BMI metabolome, and suggest new targets for researchers attempting to clarify mechanistic links between high BMIs and disease risk.

Keywords: BMI; adiposity; epidemiology; metabolomics; obesity.

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Conflict of interest statement

Disclosure of potential conflicts of interest: The authors have no conflicts of interest to report.

Figures

Figure 1

Figure 1

Effect sizes and 95 percent confidence intervals for combined associations between metabolite levels and body mass index. Results are based on a population of 947 participants (505 from PLCO, 258 from Navy, and 184 from Shanghai). Within each specific study, the association between metabolite levels and BMI was modeled using linear regression, adjusted for age, gender, current smoking status. PLCO models were additionally adjusted for study center and case status and Navy models were also adjusted for case status. The combined model was done using random effects meta-analysis. Only the metabolites that met the Bonferroni corrected threshold of statistical significance in the combined models, i.e. alpha=0.05/317=0.000158, are shown here. The overall effect size (ES)—the black square-- indicates the change in units BMI (kg/m2) per one standard deviation increase in metabolite level. The horizontal line indicates the 95 percent confidence interval of the estimate. The dotted line at zero overall ES is the line of no effect.

Figure 2

Figure 2

Pairwise correlations in the PLCO dataset for the 37 metabolites associated with BMI. A white square represents a pairwise correlation of less than 0.50, a grey square represents a correlation 0.50 to 0.69, and a black square indicates a correlation of 0.70 or greater. The red dashed line separates metabolites that had been previously reported to be associated with BMI (top and/or left) vs. metabolites that had never before been reported to be associated with BMI.

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