TY - JOUR
T1 - Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis
AU - Vechetti, Ivan J.
AU - Peck, Bailey D.
AU - Wen, Yuan
AU - Walton, R. Grace
AU - Valentino, Taylor R.
AU - Alimov, Alexander P.
AU - Dungan, Cory M.
AU - Van Pelt, Douglas W.
AU - von Walden, Ferdinand
AU - Alkner, Björn
AU - Peterson, Charlotte A.
AU - McCarthy, John J.
N1 - Publisher Copyright:
© 2021 Federation of American Societies for Experimental Biology
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - adipose tissue
KW - extracellular vesicles
KW - lipolysis
KW - microRNAs
KW - skeletal muscle
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U2 - 10.1096/fj.202100242R
DO - 10.1096/fj.202100242R
M3 - Article
C2 - 34033143
AN - SCOPUS:85106903442
SN - 0892-6638
VL - 35
JO - FASEB Journal
JF - FASEB Journal
IS - 6
M1 - e21644
ER -