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

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

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2021-05-26)
Ivan J Vechetti, Bailey D Peck, Yuan Wen, R Grace Walton, Taylor R Valentino, Alexander P Alimov, Cory M Dungan, Douglas W Van Pelt, Ferdinand von Walden, Björn Alkner, Charlotte A Peterson, John J McCarthy
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.

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