期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 48, 页码 30335-30343出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2016112117
关键词
HIIT; insulin sensitivity; exosome; miRNA; FoxO1
资金
- Grant European Foundation for the Study of Diabetes (EFSD)/Lilly-2013
- Menarini
- Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM)
- Fundacio l'Academia
- Departament d'Universitats, Recerca i Societat de la Informacio (DURSI) [2017_SGR]
- Spanish Ministerio de Economia, Industria y Competitividad (MINECO) [BFU2017-89336-R]
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 by exercise and induce expression changes in the liver that impact whole-body metabolic profile.
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