Moore, S C, et al., Human Metabolic Correlates of Body Mass Index. Metabolomics, 2013.
A high body mass index (BMI) is a major riskf actor for several chronic diseases, but the biology underlyingthese associations is not well-understood. Dyslipidemia,inflammation, and elevated levels of growth factors andsex steroid hormones explain some of the increased diseaserisk, but other metabolic factors not yet identified may alsoplay a role. In order to discover novel metabolic biomarkersof BMI, we used non-targeted metabolomics to assay 317 metabolites in blood samples from 947 participants andexamined the cross-sectional associations between metabolitelevels and BMI. Participants were from three studies inthe 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 gaschromatography coupled with mass spectrometry. Weevaluated 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 acidneurotransmitter, and butyrylcarnitine, a lipid marker ofwhole-body fatty acid oxidation. Heterogeneity by study wasminimal (all Pheterogeneity[0.05). In total, 110 metaboliteswere associated with BMI at the P\0.05 level. Thesefindings establish a baseline for the BMI metabolome, andsuggest new targets for researchers attempting to clarifymechanistic links between BMI and disease risk.