Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis

Jr. Vechetti I. J., B. D. Peck, Y. Wen, R. G. Walton, T. R. Valentino, A. P. Alimov, C. M. Dungan, D. W. Van Pelt, F. von Walden, B. Alkner, C. A. Peterson, J. J. McCarthy

Research output: Contribution to journalArticlepeer-review


How regular physical activity is able to improve health remains poorly understood. The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing muscle-specific miR-1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR-1 promoted adrenergic signaling and lipolysis by targeting Tfap2alpha, a known repressor of Adrbeta3 expression. Inhibiting EV release prevented the MOV-induced increase in eWAT miR-1 abundance and expression of lipolytic genes. Resistance exercise decreased skeletal muscle miR-1 expression with a concomitant increase in plasma EV miR-1 abundance, suggesting a similar mechanism may be operative in humans. Altogether, these findings demonstrate that skeletal muscle promotes metabolic adaptations in adipose tissue in response to MOV via EV-mediated delivery of miR-1.
Original languageAmerican English
Pages (from-to)e21644
JournalFASEB Journal
Issue number6
StatePublished - 2021

Bibliographical note

Vechetti, Ivan J Jr Peck, Bailey D Wen, Yuan Walton, R Grace Valentino, Taylor R Alimov, Alexander P Dungan, Cory M Van Pelt, Douglas W von Walden, Ferdinand Alkner, Bjorn Peterson, Charlotte A McCarthy, John J eng R01 DK119619/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't FASEB J. 2021 Jun;35(6):e21644. doi: 10.1096/fj.202100242R.


  • Adipose Tissue, White/*physiopathology Adolescent Adult Animals *Exercise Extracellular Vesicles/*physiology Female Gene Expression Regulation Humans *Lipolysis Male Mice Mice, Inbred C57BL MicroRNAs/*genetics Middle Aged Muscle, Skeletal/*physiopathology *Stress, Mechanical Transcription Factor AP-2/genetics/*metabolism Young Adult *adipose tissue *extracellular vesicles *microRNAs *skeletal muscle


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