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

Authors

Ivan J. Vechetti jr, University of Nebraska-LincolnFollow
Bailey D. Peck, University of Kentucky
Yuan Wen, University of Nebraska-Lincoln
R Grace Walton, University of Kentucky
Taylor R. Valentino, University of Kentucky
Alexander P. Alimov, University of Kentucky
Cory M. Dungan, University of Kentucky
Douglas W. Van Pelt, University of Kentucky
Ferdinand von Walden, Karolinska Institute
Bjorn Alkner, Karolinska Institute
Charlotte A. Peterson, University of Kentucky
John J. McCarthy, University of Kentucky

Document Type

Article

Citation

FASEB J. 2021 June ; 35(6): e21644. doi:10.1096/fj.202100242R

Abstract

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 Tfap2α, a known repressor of Adrβ3 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.