Figure 1.

Panel (A) includes a schematic of the study design. Panel (B) includes a Venn diagram illustrating the overlap of statistically significant (at FDR 5%) associations of resting metabolites with MVPA, steps/day, and SED (N=1062; linear models relating metabolite [dependent variable] to PA measure with adjustment for age, sex, location, season, and device wear time). Metabolite levels were log-transformed and rank-normalized (resulting in mean=0 and SD=1) for analysis. In Panel (C), the regression coefficients from individual associations of metabolites and MVPA, steps/day, and SED are shown for all metabolites associated with ≥2 PA measures, in a Heatmap format. The “*” indicates associations that are statistically significant (at FDR 5%). Panel (D) shows a Venn diagram displaying statistically significant associations (at FDR 5%) of metabolites with MVPA, associations of resting metabolites with peak VO₂ (N=471, from prior report³; linear models relating peak VO₂ [dependent variable] to metabolite with adjustment for age and sex), and change in metabolite level from rest to peak exercise (N=411, from prior report³; the log₂ fold change in metabolite levels were assessed using 2-tailed t-tests). Panel (E), metabolites were plotted according to their association with MVPA (X-axis), association with peak VO₂ (Y-axis) and their exercise-induced change (circle). The circle size reflects the magnitude of change from rest to peak exercise (expressed as the absolute value of the mean log₂[peak/rest] ratio), and the coloring of the dot and the label reflect the magnitude and direction of change in the log₂[peak/rest] ratio. The 66 individual metabolites with statistically significant (at FDR 5%) associations with MVPA and peak VO₂ and with significant changes with exercise are labeled. Abbreviations: SED, sedentary time; MVPA, moderate-vigorous physical activity.