Abstract

Routine endurance exercise confers numerous health benefits, and high intensity exercise may accelerate and magnify many of these benefits. To date, explanatory molecular mechanisms and the influence of exercise intensity remain poorly understood. Circulating factors are hypothesized to transduce some of the systemic effects of exercise. We sought to examine the role of exercise and exercise intensity on the human plasma proteome. We employed an aptamer-based method to examine 1,305 plasma proteins in 12 participants before and after exercise at two physiologically defined intensities (moderate and high) to determine the proteomic response. We demonstrate that the human plasma proteome is responsive to acute exercise in an intensity-dependent manner with enrichment analysis suggesting functional biological differences between the moderate and high intensity doses. Through integration of available genetic data, we estimate the effects of acute exercise on exercise-associated traits and find proteomic responses that may contribute to observed clinical effects on coronary artery disease and blood pressure regulation. In sum, we provide supportive evidence that moderate and high intensity exercise elicit different signaling responses, that exercise may act in part non-cell autonomously through circulating plasma proteins, and that plasma protein dynamics can simulate some the beneficial and adverse effects of acute exercise.

Highlights

  • Routine endurance exercise confers numerous health benefits, and high intensity exercise may accelerate and magnify many of these benefits

  • We identified genetic loci simultaneously associated with circulating protein levels and with important clinical phenotypes from genome wide association studies (GWAS) to estimate the predicted effect of exercise on relevant human traits

  • The human plasma proteome is responsive to acute exercise in an intensitydependent manner

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Summary

Introduction

Routine endurance exercise confers numerous health benefits, and high intensity exercise may accelerate and magnify many of these benefits. We employed an aptamer-based method to examine 1,305 plasma proteins in 12 participants before and after exercise at two physiologically defined intensities (moderate and high) to determine the proteomic response. We demonstrate that the human plasma proteome is responsive to acute exercise in an intensity-dependent manner with enrichment analysis suggesting functional biological differences between the moderate and high intensity doses. Through integration of available genetic data, we estimate the effects of acute exercise on exercise-associated traits and find proteomic responses that may contribute to observed clinical effects on coronary artery disease and blood pressure regulation. We provide supportive evidence that moderate and high intensity exercise elicit different signaling responses, that exercise may act in part non-cell autonomously through circulating plasma proteins, and that plasma protein dynamics can simulate some the beneficial and adverse effects of acute exercise. Plasma-based proteins play fundamental roles in numerous biological processes including growth, repair, and signaling in both disease and ­health[21] and may facilitate exercise-induced cellular, metabolic, and physiologic ­changes[12]

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