Human metabolic correlates of body mass index
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 P heterogeneity > 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.
KeywordsBMI Adiposity Metabolomics Epidemiology Obesity
We thank David P. Check of the Division of Cancer Epidemiology and Genetics of the U.S. National Cancer Institute for preparation of the figures and Nathan Appel, Dominick Parisi, and Adam Risch of Information Management Services for programming support. Finally, we thank the participants for their involvement in our research studies. This work was supported, in part, by the Breast Cancer Research Stamp Fund, awarded through competitive peer review and the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The Shanghai Women’s Health Study was supported primarily by R37CA70867 and the Shanghai Men’s Health Study was supported by R01CA082729.
Conflict of interest
The authors have no conflict of interest to report.
- Evans, A. M., Dehaven, C. D., Barrett, T., Mitchell, M., & Milgram, E. (2009). Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems. Analytical Chemistry, 81(16), 6656–6667.CrossRefPubMedGoogle Scholar
- National Cancer Institute. Provocative Questions Project. http://provocativequestions.nci.nih.gov/rfa. Accessed March 11, 2013.
- Poirier, P., Giles, T. D., Bray, G. A., et al. (2006). Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation, 113(6), 898–918.CrossRefPubMedGoogle Scholar