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

Proceedings of the National Academy of Sciences of the United States of America
Carlos CastañoMarcelina Párrizas

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 in miR-133a and miR-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 of FoxO1 is decreased in the liver of trained and exosome-treated mice. Treatment with exosomes transfected with a miR-133b mimic or with a specific siRNA targeting FoxO1 recapitulates 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 ...Continue Reading

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Citations

Jun 29, 2021·American Journal of Physiology. Endocrinology and Metabolism·Juulia H LautaojaJuha J Hulmi
Aug 8, 2021·International Journal of Molecular Sciences·Ainhoa AlberroDavid Otaegui
Aug 28, 2021·Cells·Alejandra Romero, Juergen Eckel
Aug 16, 2021·The Journal of Physiology·Bruna Brasil BrandaoC Ronald Kahn
Aug 31, 2021·Frontiers in Physiology·Aurel B LeuchtmannChristoph Handschin

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