Extracellular Vesicle miR-1 Delivery from Skeletal Muscle to Adipose Tissue Modifies Lipolytic Pathways in Response to Resistance Exercise in Humans

Extracellular vesicles (EVs) have emerged as important mediators of inter-tissue signaling and exercise adaptations. In this human study (n=32), muscle-specific microRNA-1 (miR-1) was delivered 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 CAV2 and TRIM6 as miR-1 target genes upregulated in adipose tissue of participants with high increases in miR-1 levels following resistance exercise. 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 novel mechanism by which skeletal muscle communicates to adipose tissue and modulates lipolysis via delivery of miR-1-containing EVs.