Metabolic Profiling of Total Physical Activity and Sedentary Behavior in Community-Dwelling Men

PLoS One. 2016 Oct 14;11(10):e0164877. doi: 10.1371/journal.pone.0164877. eCollection 2016.


Objective: Physical activity is known to be preventive against various non-communicable diseases. We investigated the relationship between daily physical activity level and plasma metabolites using a targeted metabolomics approach in a population-based study.

Methods: A total of 1,193 participants (male, aged 35 to 74 years) with fasting blood samples were selected from the baseline survey of a cohort study. Information on daily total physical activity, classified into four levels by quartile of metabolic equivalent scores, and sedentary behavior, defined as hours of sitting per day, was collected through a self-administered questionnaire. Plasma metabolite concentrations were quantified by capillary electrophoresis mass spectrometry method. We performed linear regression analysis models with multivariable adjustment and corrected p-values for multiple testing in the original population (n = 808). The robustness of the results was confirmed by replication analysis in a separate population (n = 385) created by random allocation.

Results: Higher levels of total physical activity were associated with various metabolite concentrations, including lower concentrations of amino acids and their derivatives, and higher concentrations of pipecolate (FDR p <0.05 in original population). The findings persisted after adjustment for age, body mass index, smoking, alcohol intake, and energy intake. Isoleucine, leucine, valine, 4-methyl-2-oxoisopentanoate, 2-oxoisopentanoate, alanine, and proline concentrations were lower with a shorter sitting time.

Conclusions: Physical activity is related to various plasma metabolites, including known biomarkers for future insulin resistance or type 2 diabetes. These metabolites might potentially play a key role in the protective effects of higher physical activity and/or less sedentary behavior on non-communicable diseases.

MeSH terms

  • Adult
  • Aged
  • Amino Acids / blood
  • Biomarkers / blood*
  • Electrophoresis, Capillary
  • Hemiterpenes
  • Humans
  • Keto Acids / blood
  • Male
  • Mass Spectrometry
  • Metabolomics*
  • Middle Aged
  • Motor Activity
  • Sedentary Behavior*
  • Self Report
  • Surveys and Questionnaires


  • Amino Acids
  • Biomarkers
  • Hemiterpenes
  • Keto Acids
  • alpha-ketoisovalerate
  • alpha-ketoisocaproic acid

Grant support

This work was supported in part by research funds from the Yamagata Prefectural Government and the city of Tsuruoka and by the Grant-in-Aid for Scientific Research (grant numbers 24390168 and 15H04778) from the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.