American journal of physiology. Cell physiologyDec 15, 2021

Tissue differences in cell particle release outside the body and muscle fiber particles entering the bloodstream in living animals

Updated Mar 3, 2026

Abstract

Skeletal muscle tissue secretes more extracellular vesicles (EVs) than white adipose tissue.

Differences in EV secretion between skeletal muscle and white adipose tissue are not due to muscle contraction.
The difference in EV abundance may be linked to variations in the metabolic capacity of the tissues.
A dual fluorescent reporter mouse model confirmed that skeletal muscle myofibers are a significant source of EVs.
Approximately 5% of circulating tetraspanin-positive EVs are derived from skeletal muscle myofibers.
Skeletal muscle myofiber-derived EVs can reach the circulation in vivo.

Simplified

Extracellular vesicles (EVs) are biomarkers and modifiers of human disease. EVs secreted by insulin-responsive tissues like skeletal muscle (SkM) and white adipose tissue (WAT) contribute to metabolic health and disease but the relative abundance of EVs from these tissues has not been directly examined. Human Protein Atlas data and directly measuring EV secretion in mouse SkM and WAT using an ex vivo tissue explant model confirmed that SkM tissue secretes more EVs than WAT. Differences in EV secretion between SkM and WAT were not due to SkM contraction but may be explained by differences in tissue metabolic capacity. We next examined how many EVs secreted from SkM tissue ex vivo and in vivo are myofiber-derived. To do this, a SkM myofiber-specific dual fluorescent reporter mouse was created. Spectral flow cytometry revealed that SkM myofibers are a major source of SkM tissue-derived EVs ex vivo and EV immunocapture indicates that ∼5% of circulating tetraspanin-positive EVs are derived from SkM myofibers in vivo. Our findings demonstrate that) SkM secretes more EVs than WAT,) many SkM tissue EVs are derived from SkM myofibers, and) SkM myofiber-derived EVs reach the circulation in vivo. These findings advance our understanding of EV secretion between metabolically active tissues and provide direct evidence that SkM myofibers secrete EVs that can reach the circulation in vivo. 1 2 3

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