Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis.
Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis.
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机械超载引起的肌肉衍生的细胞外囊泡促进脂肪组织脂解。
DOI：
10.1096/fj.202100242r
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
McCarthy JJ
中科院分区：
文献类型：
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作者：
Vechetti IJ Jr;Peck BD;Wen Y;Walton RG;Valentino TR;Alimov AP;Dungan CM;Van Pelt DW;von Walden F;Alkner B;Peterson CA;McCarthy JJ
定期的身体活动如何能够改善健康仍然知之甚少。运动后骨骼肌释放因子被认为是介导这种全身益处的可能机制。我们描述了一种机制，其中骨骼肌，在响应机械过载（MOV）诱导的肥大刺激，释放细胞外囊泡（EV）含有肌肉特异性的miR-1，优先采取的皮下白色脂肪组织（eWAT）。在eWAT中，miR-1通过靶向Tfap 2 α（一种已知的Adrβ3表达抑制剂）促进肾上腺素能信号传导和脂解。抑制EV释放阻止了MOV诱导的eWAT miR-1丰度和脂解基因表达的增加。抗阻运动降低了骨骼肌miR-1的表达，同时增加了血浆EV miR-1的丰度，这表明在人类中可能存在类似的机制。总之，这些发现表明，骨骼肌通过EV介导的miR-1递送促进脂肪组织响应MOV的代谢适应。
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.