Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise

Martin Whitham, Benjamin L. Parker, Martin Friedrichsen, Janne R. Hingst, Marit Hjorth, William E. Hughes, Casey L. Egan, Lena Cron, Kevin I. Watt, Rhiannon P. Kuchel, Navind Jayasooriah, Emma Estevez, Tim Petzold, Catherine M. Suter, Paul Gregorevic, Bente Kiens, Erik A. Richter, David E. James, Jørgen F.P. Wojtaszewski, Mark A. Febbraio

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358 Citations (Scopus)


Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative proteomic techniques to characterize the exercise-induced secretion of EV-contained proteins. Following a 1-hr bout of cycling exercise in healthy humans, we observed an increase in the circulation of over 300 proteins, with a notable enrichment of several classes of proteins that compose exosomes and small vesicles. Pulse-chase and intravital imaging experiments suggested EVs liberated by exercise have a propensity to localize in the liver and can transfer their protein cargo. Moreover, by employing arteriovenous balance studies across the contracting human limb, we identified several novel candidate myokines, released into circulation independently of classical secretion. These data identify a new paradigm by which tissue crosstalk during exercise can exert systemic biological effects. Using quantitative proteomic techniques and intravital imaging experiments, Whitham et al. characterize the exercise-induced secretion of proteins contained in extracellular vesicles (EVs) and identify several novel candidate myokines that are released into the circulation independently of classical secretion.

Original languageEnglish
Pages (from-to)237-251
Number of pages15
JournalCell Metabolism
Issue number1
Publication statusPublished - 9 Jan 2018


  • arteriovenous
  • exercise
  • exosome
  • extracellular vesicle
  • integrin
  • muscle
  • myokine
  • proteomics

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