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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish
Article numbere21644
JournalFASEB Journal
Volume35
Issue number6
DOIs
StatePublished - Jun 2021

Bibliographical note

Funding Information:
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. R01DK119619) to CAP and JJM and Futurum—the Academy for Health and Care, Region Jönköping County to BA and the Swedish Research Council for Sports Science to FVW. The authors also thank Dr Beibei Zhu for his input and guidance on the 3T3‐L1 cell culture.

Funding Information:
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. R01DK119619) to CAP and JJM and Futurum?the Academy for Health and Care, Region J?nk?ping County to BA and the Swedish Research Council for Sports Science to FVW. The authors also thank Dr Beibei Zhu for his input and guidance on the 3T3-L1 cell culture.

Publisher Copyright:
© 2021 Federation of American Societies for Experimental Biology

Keywords

  • adipose tissue
  • extracellular vesicles
  • lipolysis
  • microRNAs
  • skeletal muscle

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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