Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise

Safdar, Adeel; Tarnopolsky, Mark A.

doi:10.1101/cshperspect.a029827

PreprintCited by 203Extracellular vesicles in diseaseExercise and Physiological ResponsesCardiovascular and exercise physiology

Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise

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Safdar, Adeel, Tarnopolsky, Mark A.·2018·Cold Spring Harbor Perspectives in Medicine

DOI 10.1101/cshperspect.a029827PMC PMC5830902

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Abstract

Habitual endurance exercise training is associated with multisystemic metabolic adaptations that lower the risk of inactivity-associated disorders such as obesity and type 2 diabetes mellitus (T2DM). Identification of complex systemic signaling networks responsible for these benefits are of great interest because of their therapeutic potential in metabolic diseases; however, specific signals that modulate the multisystemic benefits of exercise in multiple tissues and organs are only recently being discovered. Accumulated evidence suggests that muscle and other tissues have an endocrine function and release peptides and nucleic acids into the circulation in response to acute endurance exercise to mediate the multisystemic adaptations. Factors released from skeletal muscle have been termed myokines and we propose that the total of all factors released in response to endurance exercise (including peptides, nucleic acids, and metabolites) be termed, "exerkines." We propose that many of the exerkines are released within extracellular vesicles called exosomes, which regulate peripheral organ cross talk. Exosomes (30-140 nm) and larger microvesicles [MVs] (100-1000 nm) are subcategories of extracellular vesicles that are released into the circulation. Exosomes contain peptides and several nucleic acids (microRNA [miRNA], messenger RNA [mRNA], mitochondrial DNA [mtDNA]) and are involved in intercellular/tissue exchange of their contents. An acute bout of endurance exercise increases circulating exosomes that are hypothesized to mediate organ cross talk to promote systemic adaptation to endurance exercise. Further support for the role of exosomes (and possibly MVs) in mediating the systemic benefits of exercise comes from the fact that the majority of the previously reported myokines/exerkines are found in extracellular vesicles databases (Vesiclepedia and ExoCarta). We propose that exosomes isolated from athletes following exercise or exosomes bioengineered to incorporate one or many of known exerkines will be therapeutically useful in the treatment of obesity, T2DM, and other aging-associated metabolic disorders.

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Extracellular vesicles are membranous structures released from almost all cell types with cell-specific profiles, ranging in size from 150 to 1,000 nm and carrying proteins, nucleic acids and lipids.
“Extracellular vesicles are membranous structures that are released from almost all cell types, with cell-specific profiles. They vary in size, ranging from 150 nm to 1,000 nm, and carry an assortment of material, including proteins, nucleic acids and lipids18,34.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [34]
MicroRNAs may exert endocrine effects through extracellular vesicle-based transport.
“supporting the possibility of microRNAs exerting their endocrine effects via extracellular vesicle-based transport11,34.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [34]

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RETRACTED: Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice
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RETRACTED ARTICLE:Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice
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Physical Activity and Cancer Outcomes: A Precision Medicine Approach
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Effective isolation of exosomes with polyethylene glycol from cell culture supernatant for in-depth proteome profiling
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The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor?
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Physical Training Increases Muscle GLUT4 Protein and mRNA in Patients With NIDDM
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miRNA in the Regulation of Skeletal Muscle Adaptation to Acute Endurance Exercise in C57Bl/6J Male Mice
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Edward F. Adolph Distinguished Lecture: Muscle as an endocrine organ: IL-6 and other myokines
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Proteomic Analysis of C2C12 Myoblast and Myotube Exosome-Like Vesicles: A New Paradigm for Myoblast-Myotube Cross Talk?
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Circulating miR-192 and miR-193b Are Markers of Prediabetes and Are Modulated by an Exercise Intervention
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IL-6 Induced STAT3 Signalling Is Associated with the Proliferation of Human Muscle Satellite Cells Following Acute Muscle Damage
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The microRNA Signature in Response to Insulin Reveals Its Implication in the Transcriptional Action of Insulin in Human Skeletal Muscle and the Role of a Sterol Regulatory Element–Binding Protein-1c/Myocyte Enhancer Factor 2C Pathway
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Effects of Exercise on microRNA Expression in Young Males Peripheral Blood Mononuclear Cells
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Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response
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Muscle–Organ Crosstalk: The Emerging Roles of Myokines
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“It has been proposed that the total sum of all exercise-induced factors (such as peptides and nucleic acids) released from muscle and other organs into the blood should be named “exerkines” (8, 9).”
Background
Exerkines in health, resilience and disease
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Molecular Responses to Acute Exercise and Their Relevance for Adaptations in Skeletal Muscle to Exercise Training
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Small peptides: Could they have a big role in metabolism and the response to exercise?
Atakan, M. M., Türkel, İ., Özerkliğ, B., Koşar, Ş. N., Taylor, D. F., Yan, X., & Bishop, D. J. (2024) · The Journal of Physiology · doi:10.1113/jp283214 · Cited by 13 · see citing works

Authors: Safdar, A., & Tarnopolsky, M. A.
Affiliations: McMaster University (CA)
ORCID: Safdar, Adeel
Tarnopolsky, Mark A.
Venue: Cold Spring Harbor Perspectives in Medicine
Publisher: Cold Spring Harbor Laboratory
Published: 2017-05-10
Volume: 8
Issue: 3
Pages: a029827
ISSN: 2157-1422 (ISSN-L)
DOI: 10.1101/cshperspect.a029827
PMC: PMC5830902
OpenAlex: W2613327265
Cited by: 203
References: 223
Citations by year: 2026: 28 · 2025: 26 · 2024: 21 · 2023: 23 · 2022: 28 · 2021: 34 · 2020: 20 · 2019: 16 · 2018: 5 · 2017: 2
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Cold Spring Harbor Perspectives in Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of Canada
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords: exosomes, exerkines, myokines, endurance exercise, extracellular vesicles, microvesicles, organ crosstalk, skeletal muscle endocrine function, microRNA, mitochondrial DNA, obesity, type 2 diabetes, exercise therapy
MeSH terms: Extracellular Vesicles, Adaptation, Physiological, Diabetes Mellitus, Type 2, Humans, Metabolic Diseases, Obesity, Physical Endurance, Exercise, Muscle, Skeletal, Exosomes

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Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise

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