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

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.

SUBMITTER: Vechetti IJ

PROVIDER: S-EPMC8607211 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Vechetti Ivan J IJ Peck Bailey D BD Wen Yuan Y Walton R Grace RG Valentino Taylor R TR Alimov Alexander P AP Dungan Cory M CM Van Pelt Douglas W DW von Walden Ferdinand F Alkner Björn B Peterson Charlotte A CA McCarthy John J JJ

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20210601 6

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 e ...[more]

PMID: 34033143

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Project description:Background: Treatment of diabetic wounds is a major challenge in clinical practice. Extracellular vesicles (EVs) from adipose-derived stem cells have shown effectiveness in diabetic wound models. However, obtaining ADSC-EVs requires culturing vast numbers of cells, which is hampered by the need for expensive equipment and reagents, extended time cost, and complicated procedures before commercialization. Therefore, methods to extract EVs from discarded tissue need to be developed, for immediate application during surgery. For this reason, mechanical, collagenase-digestive, and constant in-vitro-collective methods were designed and compared for preparing therapy-grade EVs directly from adipose tissue. Methods: Characteristics and quantities of EVs were detected by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting firstly. To investigate the biological effects of EVs on diabetic wound healing, angiogenesis, proliferation, migration, and inflammation-regulation assays were then evaluated in vitro, along with a diabetic wound healing mouse model in vivo. To further explore the potential therapeutic mechanism of EVs, miRNA expression profile of EVs were also identified and analyzed. Results: The adipose tissue derived EVs (AT-EVs) were showed to qualify ISEV identification by nanoparticle tracking analysis and Western blotting and the AT-EVs yield from three methods was equal. EVs also showed promoting effects on biological processes related to diabetic wound healing, which depend on fibroblasts, keratinocytes, endothelial cells, and macrophages both in vitro and in vivo. We also observed enrichment of overlapping or unique miRNAs originate from different types of AT-EVs associated with diabetic wound healing for further investigation. Conclusion: After comparative analyses, a mechanical method was proposed for preparing immediate clinical applicable EVs from adipose tissue that would result in reduced preparation time and lower cost, which could have promising application potential in treating diabetic wounds.

Project description:BackgroundBrown adipose tissue (BAT) is considered as a primary location of adaptive thermogenesis and the thermogenic activities of brown adipocytes are also connected to generating heat and counteracting obesity. Recent studies revealed that BAT could secrete certain batokines-like factors especially small extracellular vesicles (sEVs), which contributed to the systemic consequences of BAT activities. As a newly emerging class of mediators, some long non-coding RNAs (lncRNAs) have exhibited metabolic regulatory effects in adipocyte development. However, besides the well-studied lncRNAs, the lncRNAs carried by sEVs derived from brown adipose tissue (sEV-BAT) have not been identified yet. RESULTS: In this study, we demonstrated that sEV-BAT could induce beige adipocyte differentiation both in ASCs and 3T3-L1 cells, while sEV-WAT had no corresponding effects. The lncRNA microarray assay on sEV-WAT and sEV-BAT revealed a total of 563 types of known lncRNAs were identified to be differentially expressed, among which 232 lncRNAs were upregulated and 331 lncRNAs were downregulated in sEV-BAT. Three novel candidates (AK029592, humanlincRNA1030 and ENSMUST00000152284) were selected for further validation. LncRNA-mRNA network analysis revealed candidate lncRNAs were largely embedded in cellular metabolic pathways. During adipogenic and thermogenic phenotype differentiation in ASCs and 3T3-L1 cells, only the expressions of AK029592 were upregulated. The three lncRNAs were all relatively enriched in brown adipose tissues and brown adipocytes. In different adipocytes, sEV and adipose tissue, the expression of AK029592 and ENSMUST00000152284 were remarkably decreased in obese mice compared to lean mice, while obesity state could not change the expression of humanlincRNA1030.ConclusionCollectively, our profiling study provided a comprehensive catalog for the study of lncRNAs specifically carried by sEV-BAT and indicated the potential regulatory role of certain sEV-BAT lncRNAs in thermogenesis.

Dataset Information

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

Publications

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

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