Identification of serum analytes and metabolites associated with aerobic capacity

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ORIGINAL ARTICLE

Identification of serum analytes and metabolites associated with aerobic capacity Michael S. Lustgarten • Lori Lyn Price • Tanya Logvinenko • Christos Hatzis Nandan Padukone • Nicholas V. Reo • Edward M. Phillips • Dylan Kirn • John Mills • Roger A. Fielding



Received: 18 April 2012 / Accepted: 16 November 2012 Ó Springer-Verlag Berlin Heidelberg 2012

Abstract Studies aimed at identifying serum markers of cellular metabolism (biomarkers) that are associated at baseline with aerobic capacity (VO2max) in young, healthy individuals have yet to be reported. Therefore, the goal of the present study was to use the standard chemistry screen and untargeted mass spectrometry (MS)-based metabolomic profiling to identify significant associations between baseline levels of serum analytes or metabolites with VO2max (77 subjects, age range 18–35 years). Use of multivariable linear regression identified three analytes (standard chemistry screen) and twenty-three metabolites (MS-based metabolomics) containing significant, sex-adjusted associations with VO2max. In addition, fourteen metabolites were found to

Communicated by Martin Flueck.

Electronic supplementary material The online version of this article (doi:10.1007/s00421-012-2555-x) contains supplementary material, which is available to authorized users. M. S. Lustgarten  E. M. Phillips  D. Kirn  J. Mills  R. A. Fielding (&) Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA e-mail: [email protected] L. L. Price  T. Logvinenko Biostatistics Research Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA C. Hatzis  N. Padukone Nuvera Biosciences, Inc., Woburn, MA, USA N. V. Reo Biochemistry and Molecular Biology, Wright State University, Dayton, OH, USA

contain sex-specific associations with aerobic capacity. Subsequent stepwise multivariable linear regression identified the combination of SGOT, 4-ethylphenylsulfate, tryptophan, c-tocopherol, and a-hydroxyisovalerate as overall, sex-adjusted baseline predictors of VO2max (adjusted R2 = 0.66). However, the results of the stepwise model were found to be sensitive to outliers; therefore, random forest (RF) regression was performed. Use of RF regression identified a combination of seven covariates that explained 57.6 % of the variability inherent in VO2max. Furthermore, inclusion of significant analytes, metabolites and sex-specific metabolites into a stepwise regression model identified the combination of five metabolites in males and seven metabolites in females as being able to explain 80 and 58 % of the variability inherent in VO2max, respectively. In conclusion, the evidence presented in the current report is the first attempt to identify baseline serum biomarkers that are significantly associated with VO2max in young, healthy adult humans. Keywords

Analytes  Metabolites  VO2max

Introduction VO2max describes