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

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


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.

Keywords: adipose tissue; extracellular vesicles; lipolysis; microRNAs; skeletal muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / physiopathology*
  • Adolescent
  • Adult
  • Animals
  • Exercise*
  • Extracellular Vesicles / physiology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Lipolysis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Middle Aged
  • Muscle, Skeletal / physiopathology*
  • Stress, Mechanical*
  • Transcription Factor AP-2 / genetics
  • Transcription Factor AP-2 / metabolism*
  • Young Adult


  • MIRN1 microRNA, human
  • MicroRNAs
  • TFAP2A protein, human
  • Transcription Factor AP-2