Human metabolic correlates of body mass index

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.

Metabolomic Biomarkers for Obesity in Humans: A Short Review

“…An article by Moore et al [13] found elevations in C3-CN, C5-CN, and C6-CN, and another showed alterations in L-carnitine ( ↓ ), C3-CN ( ↑ ), and C4-CN ( ↑ ) [14] .…”

“…Papers finally included n = 13 Zeng et al [19] Pietiläinen et al [41] Oberbach et al [9] Newgard et al [12] Karlsson et al [39] Wahl et al [11] Mihalik et al [21] Kim et al [14] McCormack et al [20] Okada et al [35] Warensjö et al [38] Moore et al [13] Study design …”

“…Downloaded by: Kim et al [14] McCormack et al [20] Okada et al [35] Warensjö et al [38] Moore et al [13] Reported no differences CoA by CPT2, which is located in the inner membrane of the mitochondria. This CoA ester can then undergo β-oxidation.…”

Comparing metabolite profiles of habitual diet in serum and urine

“…Associations between dietary variables and metabolites were estimated with the use of a partial Pearson correlation while adjusting for factors previously associated with metabolites and dietary intake (27)(28)(29)(30)(31)(32)(33)(34)(35), including age (years), sex, smoking (never, past, or current), fasting status at time of blood draw (fasting or nonfasting), case-control status, BMI (kg/m 2 ), physical activity index (weekly frequency of moderate-intensity leisure activity plus 2 3 weekly frequency of vigorous-intensity leisure activity), education (#12 y, vocational or 1-3 y college, $4 y college, or graduate), and daily caloric intake (kcal/d). Analyses of single vitamin and nutrient supplement use were adjusted for multivitamin use.…”

Potential Nutrigenomic Approaches to Reduce the High Incidence of Obesity in Qatar

“…Several metabolomics studies have already been performed in the field of obesity and T2DM [76,77]. Metabolites from lipids, amino acids, and carbohydrates pathways are associated with BMI [78]. Mostly intercellular lipid intermediates, sphingolipids and bile acid intermediates are associated to obesity [77].…”