The potential of endurance exercise-derived exosomes to treat metabolic diseases
Abstract
Endurance exercise-mediated multisystemic adaptations are known to mitigate metabolism-related disorders such as obesity and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanisms that promote crosstalk between organs and orchestrate the pro-metabolic effects of endurance exercise remain unclear. Exercise-induced release of peptides and nucleic acids from skeletal muscle and other organs (collectively termed 'exerkines') has been implicated in mediating these systemic adaptations. Given that the extracellular milieu is probably not a hospitable environment for labile exerkines, a lipid vehicle-based mode of delivery has originated over the course of evolution. Two types of extracellular vesicles, exosomes and microvesicles, have been shown to contain proteins and nucleic acids that participate in a variety of physiological and pathological processes. Exosomes, in particular, have been shown to facilitate the exchange of peptides, microRNA, mRNA and mitochondrial DNA between cells and tissues. Intriguingly, circulatory extracellular vesicle content increases in an intensity-dependant manner in response to endurance exercise. We propose that the systemic benefits of exercise are modulated by exosomes and/or microvesicles functioning in an autocrine, paracrine and/or endocrine manner. Furthermore, we posit that native or modified exosomes, and/or microvesicles enriched with exerkines will have therapeutic utility in the treatment of obesity and T2DM.
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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 [11]
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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).”
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Exerkines, Nutrition, and Systemic Metabolism
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- Authors
- Safdar, A., Saleem, A., & Tarnopolsky, M. A.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Tarnopolsky, Mark A.
- Venue
- Nature Reviews Endocrinology
- Published
- 2016-05-27
- Volume
- 12
- Issue
- 9
- Pages
- 504-517
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2401918595
- Cited by
- 463
- References
- 199
- Citations by year
- 2026: 53 · 2025: 48 · 2024: 51 · 2023: 64 · 2022: 56 · 2021: 43 · 2020: 47 · 2019: 37 · 2018: 26 · 2017: 31 · 2016: 7
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- 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
- endurance exercise, exosomes, exerkines, extracellular vesicles, microvesicles, metabolic disorders, obesity, type 2 diabetes, paracrine signaling, autocrine signaling, hormone signaling, microRNA, mitochondrial DNA, exosome therapy
- MeSH terms
- Extracellular Vesicles, Animals, Diabetes Mellitus, Type 2, Humans, Metabolic Diseases, Obesity, Physical Endurance, Exercise, Muscle, Skeletal, Exosomes
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