Associations Between Body Mass Index, Physical Activity And 145 Blood Metabolites: A Targeted Metabolomic Approach In The Epic Cohort

Marion CARAYOL, International Agency for Research on Cancer, France
LEITZMANN M. 1 , FERRARI P. 1 , ZAMORA-ROS R. 1 , ACHAINTRE D. 1 , STEPIEN M. 1 , SCHMIDT J. 2 , TRAVIS R. 2 , KEY T. 2 , JENAB M. 1 , SCALBERT A. 1 , RINALDI S. 1

1 International Agency for Research on Cancer, Section of Nutrition and Metabolism, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France
2 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Purpose: Metabolomics approaches are of main interest to better characterize metabolic phenotypes of lifestyle exposures. Obesity and physical inactivity have been associated with cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The present study aimed to examine the associations of body mass index (BMI) and physical activity (PA) with 145 blood metabolites in EPIC.
Methods: Blood metabolites were measured with the Biocrates kit using tandem mass spectrometry and liquid chromatography in 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 individuals who were control subjects in a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary). Measured metabolites included acylcarnitines, amino acids, biogenic amines, hexoses, phosphatidylcholines, and sphingomyelins. Associations between metabolites concentrations and BMI and PA were assessed using linear regression models, controlling for potential confounders and multiple testing.
Results: Of the 145 quantified metabolites, 40 and 45 individual metabolites showed significant differences according to BMI variations in the EPIC-Oxford and EPIC-Hepatobiliary sub-cohorts, respectively, of which 22 metabolites were common (kynurenine, glutamate, one sphingomyelin, and 19 phosphatidylcholines). Stratification of EPIC-Oxford individuals by diet group revealed that associations of metabolites with BMI were predominantly observed in meat eaters (2 acylcarnitines, serine, 8 phosphatidylcholines) rather than fish eaters (4 phosphatidylcholines), vegetarians (one phosphatidylcholine) and vegans (none). No metabolites were consistently associated with PA in the two sub-cohorts.
Conclusions: Our findings provide new knowledge on blood metabolic signatures of BMI in European adults. These signatures made of phosphatidylcholines, sphingomyelins and kynurenine may help identifying novel mechanisms mediating the relationship of BMI with obesity-related diseases.
 
Funding source: International Agency for Research on Cancer; Fondation de France (project grant #2014-00050542); French National Cancer Institute (L’Institut National du Cancer; INCA) (grant number 2009-139; PI: M. Jenab); EPIC grants.