Abstract
Implementation of regular physical activity helps in the maintenance of a healthy metabolic profile both in humans and mice through molecular mechanisms not yet completely defined. Here, we show that high-intensity interval training (HIIT) modifies the microRNA (miRNA) profile of circulating exosomes in mice, including significant increases inmiR-133aandmiR-133b. Importantly, treatment of sedentary mice with exosomes isolated from the plasma of trained mice improves glucose tolerance, insulin sensitivity, and decreases plasma levels of triglycerides. Moreover, exosomes isolated from the muscle of trained mice display similar changes in miRNA content, and their administration to sedentary mice reproduces the improvement of glucose tolerance. Exosomal miRNAs up-regulated by HIIT target insulin-regulated transcription factor forkhead box O1 (FoxO1) and, accordingly, expression ofFoxO1is decreased in the liver of trained and exosome-treated mice. Treatment with exosomes transfected with amiR-133bmimic or with a specific siRNA targetingFoxO1recapitulates the metabolic effects observed in trained mice. Overall, our data suggest that circulating exosomes released by the muscle carry a specific miRNA signature that is modified by exercise and induce expression changes in the liver that impact whole-body metabolic profile.
Funder
European Foundation for the Study of Diabetes
Menarini
CIBERDEM
Fundacio; l'Academia
Government of Catalonia | Departament d'Universitats, Recerca i Societat de la Informació
Ministerio de Economía y Competitividad
Publisher
Proceedings of the National Academy of Sciences
Cited by
61 articles.
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