Abstract
In response to acute exercise, an array of metabolites, nucleic acids, and proteins are enriched in circulation. Collectively termed “exercise factors,” these molecules represent a topical area of research given their speculated contribution to both acute exercise metabolism and adaptation to exercise training. In addition to acute changes induced by exercise, the resting profile of circulating exercise factors may be altered by exercise training. Many exercise factors are speculated to be transported in circulation as the cargo of extracellular vesicles (EVs), and in particular, a sub-category termed “small EVs.” This review describes an overview of exercise factors, small EVs and the effects of exercise, but is specifically focused on a critical appraisal of methodological approaches and current knowledge in the context of changes in the resting profile small EVs induced by exercise training, and the potential bioactivities of preparations of these “exercise-trained” small EVs. Research to date can only be considered preliminary, with interpretation of many studies hindered by limited evidence for the rigorous identification of small EVs, and the conflation of acute and chronic responses to exercise due to sample timing in proximity to exercise. Further research that places a greater emphasis on the rigorous identification of small EVs, and interrogation of potential bioactivity is required to establish more detailed descriptions of the response of small EVs to exercise training, and consequent effects on exercise adaptation.
Highlights
When individuals undertake repeated bouts of exercise, acute molecular responses and chronic adaptive changes occur that result in functional changes at the levels of cells, tissues, organs, and systems
Appraisal of existing studies across rodents and humans regarding the influence of exercise training on the abundance of small EVs and their proposed miRNA cargoes leads us to conclude that the characterization of small EVs within samples is generally inadequate by way of employing insufficient methodological approaches
While some data indicate that the resting concentration of small EVs may change with exercise training, which has been commented by others (Brahmer et al., 2020; Nederveen et al., 2021), arguably the methods employed do not produce sufficient information to confidently state this to be the case
Summary
When individuals undertake repeated bouts of exercise (i.e., exercise training), acute molecular responses and chronic adaptive changes occur that result in functional changes at the levels of cells, tissues, organs, and systems. Some of these factors have been classified with established labels, namely “myokine” for peptides and proteins released from skeletal muscle in response to exercise (Murphy et al, 2020), and “exerkine” for protein or RNA factors enriched in response to exercise, but with ambiguous tissue origin (Safdar et al, 2016). These terms are often used interchangeably, or in a manner that is misaligned to their definition (Eckel, 2019). This approach enables acknowledgment of a variety of potential responses across molecules and conditions, without having to provide excessive clarifications or redefinitions when divergences between individual molecules are present
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