Exercise intensity modulates interorgan communication and is associated with cardiometabolic health outcomes in humans

Figures

• 

  Figure 1. Acute SIE and MIE uniquely regulate the plasma proteome (A) Experimental design for moderate-intensity exercise (MIE) and sprint-interval exercise (SIE). N = 9 and 10 male participants for MIE and SIE, respectively. (B–D) Heatmap showing Z scores of mean Olink NPX values for all differentially regulated proteins between pre and 0 h (immediately post) or 3 h (3 h post) following MIE or SIE. A scatterplot of the log fold change (logFC) for differentially regulated proteins between pre vs. 0 h and pre vs. 3 h for SIE (C) and MIE (D). (E) Plasma protein abundance of representative proteins in untrained participants following either SIE or MIE. Values are normalized protein values (NPX). Error bars indicate standard error of the mean. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. See also Figures S1 and S2.

• 

  Figure 2. The plasma metabolome following SIE and MIE (A–C) Principal component analysis of individual samples before (“pre”), immediately following (“0 h”), or 3 h following (“3 h”) SIE or MIE. N = 9 and 10 male participants for MIE or SIE, respectively. Line plots showing representative metabolites and their corresponding q value, which peaks at 0 h (B) or 3 h (C). (D) Heatmap showing all significantly changed metabolites and how they cluster by temporal expression patterns. (E) Heatmap of the intensity-dependent significantly changed metabolites. (F) Representative metabolites that were significantly changed between SIE and MIE. Error bars indicate standard error of the mean. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗∗p < 0.0001. See also Figure S3.

• 

  Figure 3. Identifying the tissue of origin for exercise-regulated plasma proteins (A and B) All organ-enriched proteins with those increased (blue bar), decreased (red bar), or no change (gray bar) at 0 h following SIE (A) and MIE (B). (C) A heatmap showing organ-enriched proteins differentially regulated at 0 h or 3 h following SIE and MIE. (D–G) Schematic of the muscle collection time points following SIE and MIE. N = 14 male participants per condition. Predicted muscle-secretory genes differentially expressed following MIE and SIE (E), SIE-only (F), or MIE-only (G). (H) Principal component analysis of the conditioned media proteome following no EPS (CTRL), simulated-MIE (S-MIE), and simulated-SIE (S-SIE). (I) A heatmap of differentially regulated proteins detected in the conditioned media, with an FDR cutoff of 0.1. (J) A scatterplot showing differentially regulated proteins between S-MIE versus CTRL and S-SIE versus CTRL. The color scheme for (E)–(G) and (J) is as follows: yellow, shared; blue, SIE-specific; red, MIE-specific. See also Figure S4.

• 

  Figure 4. Transcriptomic remodeling of adipocytes following SIE or MIE (A) Experimental design of the plasma swap with primary human adipocytes. (B) Principal component analysis of the adipocyte transcriptome with “pre” or “0 h” plasma from SIE or MIE participants. N = 5–6 plasma samples from individual participants per intensity were used. (C) A heatmap of all differentially expressed genes following SIE or MIE plasma treatment. (D) Adipocyte genes of interest and their fold change, including individual values and mean fold change across groups, following incubation with SIE or MIE plasma. (E) Gene set enrichment analysis (GSEA) of “biological pathways” for all detected genes ranked by the change in expression followed by SIE or MIE plasma-treated adipocytes. (F) Exercise schematic of adipose tissue collected before (pre) and 3 hours (3 h) following a graded treadmill exercise test. (G) Venn diagram of the DEGs from the plasma swap samples (C) and those following treadmill exercise. (H–J) A heatmap of shared DEGs from (G). Fold change across conditions for CREBRF (I) and ABHD5 (J). Error bars indicate standard error of the mean. ∗p < 0.05, ∗∗∗∗p < 0.0001. Statistical analysis for (I) and…

• 

  Figure 5. Identification of exercise-regulated proteins protective from cardiometabolic disease (A) The workflow for the identification of proteins associated with and protective from cardiometabolic disease. (B) A heatmap showing the 143 proteins with an HR/OR of less than 1 corresponding to their disease chapter. Whether a protein is significant (black) or non-significant (white) is shown on the far-left. The bar plot on the top shows how many gene are in a given category. How many categories are associated with a given gene is shown in the far-right. (C) A heatmap of proteins protective from type 2 diabetes, metabolic disorders, or obesity. The heatmap corresponds to the protein log2FC relative to the “pre” time point. The bubble plot corresponds to the degree of protection (log2_hazard ratio) and significance (−log10pval).