Title | Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Vechetti IJ, Peck BD, Wen Y, R Walton G, Valentino TR, Alimov AP, Dungan CM, Van Pelt DW, Von Walden F, Alkner B, Peterson CA, McCarthy JJ |
Journal | FASEB J |
Volume | 35 |
Issue | 6 |
Pagination | e21644 |
Date Published | 2021 06 |
ISSN | 1530-6860 |
Keywords | Adipose Tissue, White, Adolescent, Adult, Animals, Exercise, Extracellular Vesicles, Female, Gene Expression Regulation, Humans, Lipolysis, Male, Mice, Mice, Inbred C57BL, MicroRNAs, Middle Aged, Muscle, Skeletal, Stress, Mechanical, Transcription Factor AP-2, Young Adult |
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. |
DOI | 10.1096/fj.202100242R |
Alternate Journal | FASEB J |
PubMed ID | 34033143 |
Grant List | R01 DK119619 / DK / NIDDK NIH HHS / United States |