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

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 exosome...

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Detalhes bibliográficos
Autores: Castaño, Carlos, Mirasierra, Mercedes, Vallejo, Mario, Novials, Anna, Párrizas, Marcelina
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2020
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/232151
Acesso em linha:http://hdl.handle.net/10261/232151
Access Level:Acceso aberto
Palavra-chave:HIIT
Insulin sensitivity
Exosome
miRNA
FoxO1
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spelling Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in miceCastaño, CarlosMirasierra, MercedesVallejo, MarioNovials, AnnaPárrizas, MarcelinaHIITInsulin sensitivityExosomemiRNAFoxO1Implementation 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.This work was supported by Grant European Foundation for the Study of Diabetes (EFSD)/Lilly-2013, Menarini, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Fundació l’Acadèmia, Project 2017_SGR of the Departament d'Universitats, Recerca i Societat de la Informació (DURSI) (A.N.), and grant BFU2017-89336-R from Spanish Ministerio de Economía, Industria y Competitividad (MINECO) (M.V.).National Academy of Sciences (U.S.)European CommissionCentro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (España)Generalitat de CatalunyaMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/232151reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-89336-Rhttp://dx.doi.org/10.1073/pnas.2016112117Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2321512026-05-22T06:33:51Z
dc.title.none.fl_str_mv Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
title Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
spellingShingle Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
Castaño, Carlos
HIIT
Insulin sensitivity
Exosome
miRNA
FoxO1
title_short Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
title_full Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
title_fullStr Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
title_full_unstemmed Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
title_sort Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
dc.creator.none.fl_str_mv Castaño, Carlos
Mirasierra, Mercedes
Vallejo, Mario
Novials, Anna
Párrizas, Marcelina
author Castaño, Carlos
author_facet Castaño, Carlos
Mirasierra, Mercedes
Vallejo, Mario
Novials, Anna
Párrizas, Marcelina
author_role author
author2 Mirasierra, Mercedes
Vallejo, Mario
Novials, Anna
Párrizas, Marcelina
author2_role author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (España)
Generalitat de Catalunya
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv HIIT
Insulin sensitivity
Exosome
miRNA
FoxO1
topic HIIT
Insulin sensitivity
Exosome
miRNA
FoxO1
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/232151
url http://hdl.handle.net/10261/232151
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2017-89336-R
http://dx.doi.org/10.1073/pnas.2016112117
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv National Academy of Sciences (U.S.)
publisher.none.fl_str_mv National Academy of Sciences (U.S.)
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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