Internal medicine

Downregulation and upregulation

Microvesicles

Bioinformatics

Protein kinase B

Biology

Gene

Endocrinology

FOXO1

microRNA

Insulin resistance

Insulin

Exosome

Insulin sensitivity

Signal transduction

Cell biology

Extracellular vesicles

Biochemistry

Medicine

Proceedings of the National Academy of Sciences

Significance The beneficial metabolic effects of exercise are mediated at least in part by the release of soluble factors by the muscles. Exosomes, small vesicles that facilitate the exchange of biological components among cells and tissues, may constitute one of these factors. Here, we show that exercise triggers the release of exosomes by the trained muscle, carrying a specific miRNA signature that induces gene expression changes in the liver, finally contributing to increased insulin sensitivity. Molecular characterization of exercise-induced exosomal miRNAs and their effects may drive the design of novel therapeutic strategies to alleviate insulin resistance and other aging-related ailments in an increasingly older society.

Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice