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.