Extracellular Vesicle Transfer of Mir-1 to Adipose Tissue Modifies Lipolytic Pathways Following Resistance Exercise

Extracellular vesicles (EVs) have emerged as important mediators of inter-tissue signaling and exercise adaptations. In this human study (n = 32), we provide evidence that muscle-specific microRNA-1 (miR-1) was transferred to adipose tissue via EVs following an acute bout of resistance exercise. Using a multi-model machine learning automation tool, we discovered muscle primary miR-1 transcript and CD63+ EV count in circulation as top explanatory features for changes in adipose miR-1 levels in response to resistance exercise. RNA-sequencing (RNA-seq) and in-silico prediction of miR-1 target genes identified caveolin 2 (CAV2) and tripartite motif containing 6 (TRIM6) as miR-1 target genes downregulated in the adipose tissue of a subset of participants with the highest increases in miR-1 levels following resistance exercise (n = 6). Overexpression of miR-1 in differentiated human adipocyte-derived stem cells downregulated these miR-1 targets and enhanced catecholamine-induced lipolysis. These data identify a potential EV-mediated mechanism by which skeletal muscle communicates to adipose tissue and modulates lipolysis via miR-1.