Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice

Objective: The adaptive response to different models of regular exercise involves complex tissue crosstalk. Our aim was to explore the involvement of extracellular vesicle (EV) microRNAs (miRNAs) in this process, the secretory role of skeletal muscle and its functional metabolic interaction with the...

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Main Authors: Paola Pinto-Hernandez, Manuel Fernandez-Sanjurjo, Daan Paget, Xurde M. Caravia, David Roiz-Valle, Juan Castilla-Silgado, Sergio Diez-Robles, Almudena Coto-Vilcapoma, David Fernandez-Vivero, Pau Gama-Perez, Pablo M. Garcia-Roves, Carlos Lopez-Otin, Juleen R. Zierath, Anna Krook, Benjamin Fernandez-Garcia, Cristina Tomas-Zapico, Eduardo Iglesias-Gutierrez
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Molecular Metabolism
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Online Access:http://www.sciencedirect.com/science/article/pii/S2212877825000808
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author Paola Pinto-Hernandez
Manuel Fernandez-Sanjurjo
Daan Paget
Xurde M. Caravia
David Roiz-Valle
Juan Castilla-Silgado
Sergio Diez-Robles
Almudena Coto-Vilcapoma
David Fernandez-Vivero
Pau Gama-Perez
Pablo M. Garcia-Roves
Carlos Lopez-Otin
Juleen R. Zierath
Anna Krook
Benjamin Fernandez-Garcia
Cristina Tomas-Zapico
Eduardo Iglesias-Gutierrez
author_facet Paola Pinto-Hernandez
Manuel Fernandez-Sanjurjo
Daan Paget
Xurde M. Caravia
David Roiz-Valle
Juan Castilla-Silgado
Sergio Diez-Robles
Almudena Coto-Vilcapoma
David Fernandez-Vivero
Pau Gama-Perez
Pablo M. Garcia-Roves
Carlos Lopez-Otin
Juleen R. Zierath
Anna Krook
Benjamin Fernandez-Garcia
Cristina Tomas-Zapico
Eduardo Iglesias-Gutierrez
author_sort Paola Pinto-Hernandez
collection DOAJ
description Objective: The adaptive response to different models of regular exercise involves complex tissue crosstalk. Our aim was to explore the involvement of extracellular vesicle (EV) microRNAs (miRNAs) in this process, the secretory role of skeletal muscle and its functional metabolic interaction with the liver. Methods: Plasma EV miRNAs obtained from mice after 4-weeks of endurance or resistance training were sequenced. Subsequent experiments using trained genetically modified mouse models and in vitro approaches involving knock-down and electrostimulated cells, were conducted. Results: Resistance training increased the expression of a group of 11 miRNAs functionally divided into two clusters. Among them, miR-29a-3p emerges as a molecular mediator released in EVs by skeletal muscle, with a relevant role in adaptation to endurance training, by contributing to modulate the expression and secretion of other miRNAs associated with training and regulating processes related to substrate availability, transport, and metabolic use in skeletal muscle and liver. Conclusions: Our study suggests that miR-29a-3p is a training-induced molecular mediator in the response and adaptation to resistance training, possibly due to its regulatory role in energy metabolism in skeletal muscle in response to exercise.
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spelling doaj-art-471ceeed96d548fdbfb653dcef6459912025-08-20T02:40:21ZengElsevierMolecular Metabolism2212-87782025-08-019810217310.1016/j.molmet.2025.102173Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in micePaola Pinto-Hernandez0Manuel Fernandez-Sanjurjo1Daan Paget2Xurde M. Caravia3David Roiz-Valle4Juan Castilla-Silgado5Sergio Diez-Robles6Almudena Coto-Vilcapoma7David Fernandez-Vivero8Pau Gama-Perez9Pablo M. Garcia-Roves10Carlos Lopez-Otin11Juleen R. Zierath12Anna Krook13Benjamin Fernandez-Garcia14Cristina Tomas-Zapico15Eduardo Iglesias-Gutierrez16Department of Functional Biology, Area of Physiology, University of Oviedo, Oviedo, Asturias, 33006, Spain; Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, 33011, SpainDepartment of Functional Biology, Area of Physiology, University of Oviedo, Oviedo, Asturias, 33006, Spain; Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, 33011, Spain; Corresponding author. Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, 33011, Spain.Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USADepartment of Biochemistry and Molecular Biology. University Institute of Oncology, University of Oviedo, Oviedo, Asturias, 33006, SpainDepartment of Functional Biology, Area of Physiology, University of Oviedo, Oviedo, Asturias, 33006, Spain; Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, 33011, SpainDepartment of Functional Biology, Area of Physiology, University of Oviedo, Oviedo, Asturias, 33006, SpainDepartment of Functional Biology, Area of Physiology, University of Oviedo, Oviedo, Asturias, 33006, SpainDepartment of Functional Biology, Area of Physiology, University of Oviedo, Oviedo, Asturias, 33006, Spain; Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, 33011, SpainDepartment of Physiological Sciences II, Faculty of Medicine-University of Barcelona, Hospitalet del Llobregat, Barcelona, SpainUniversity of Barcelona, Barcelona, Spain; Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, SpainDepartment of Biochemistry and Molecular Biology. University Institute of Oncology, University of Oviedo, Oviedo, Asturias, 33006, SpainDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, SwedenDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, SwedenHealth Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, 33011, Spain; Department of Morphology and Cell Biology, Anatomy, University of Oviedo, Oviedo, 33006, SpainDepartment of Functional Biology, Area of Physiology, University of Oviedo, Oviedo, Asturias, 33006, Spain; Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, 33011, SpainDepartment of Functional Biology, Area of Physiology, University of Oviedo, Oviedo, Asturias, 33006, Spain; Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Asturias, 33011, Spain; Corresponding author. Department of Functional Biology (Physiology), University of Oviedo, Avda. Julián Clavería 6, Oviedo, Asturias, 33006, Spain.Objective: The adaptive response to different models of regular exercise involves complex tissue crosstalk. Our aim was to explore the involvement of extracellular vesicle (EV) microRNAs (miRNAs) in this process, the secretory role of skeletal muscle and its functional metabolic interaction with the liver. Methods: Plasma EV miRNAs obtained from mice after 4-weeks of endurance or resistance training were sequenced. Subsequent experiments using trained genetically modified mouse models and in vitro approaches involving knock-down and electrostimulated cells, were conducted. Results: Resistance training increased the expression of a group of 11 miRNAs functionally divided into two clusters. Among them, miR-29a-3p emerges as a molecular mediator released in EVs by skeletal muscle, with a relevant role in adaptation to endurance training, by contributing to modulate the expression and secretion of other miRNAs associated with training and regulating processes related to substrate availability, transport, and metabolic use in skeletal muscle and liver. Conclusions: Our study suggests that miR-29a-3p is a training-induced molecular mediator in the response and adaptation to resistance training, possibly due to its regulatory role in energy metabolism in skeletal muscle in response to exercise.http://www.sciencedirect.com/science/article/pii/S2212877825000808microRNAsExercise trainingmiR-29 familyExtracellular vesiclesEnergy metabolism
spellingShingle Paola Pinto-Hernandez
Manuel Fernandez-Sanjurjo
Daan Paget
Xurde M. Caravia
David Roiz-Valle
Juan Castilla-Silgado
Sergio Diez-Robles
Almudena Coto-Vilcapoma
David Fernandez-Vivero
Pau Gama-Perez
Pablo M. Garcia-Roves
Carlos Lopez-Otin
Juleen R. Zierath
Anna Krook
Benjamin Fernandez-Garcia
Cristina Tomas-Zapico
Eduardo Iglesias-Gutierrez
Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice
Molecular Metabolism
microRNAs
Exercise training
miR-29 family
Extracellular vesicles
Energy metabolism
title Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice
title_full Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice
title_fullStr Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice
title_full_unstemmed Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice
title_short Training-induced plasma miR-29a-3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice
title_sort training induced plasma mir 29a 3p is secreted by skeletal muscle and contributes to metabolic adaptations to resistance exercise in mice
topic microRNAs
Exercise training
miR-29 family
Extracellular vesicles
Energy metabolism
url http://www.sciencedirect.com/science/article/pii/S2212877825000808
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