Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.

Background Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently,...

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Autores: Orozco‑Aguilar, Josué, Tacchi, Franco, Aguirre, Francisco, Valero‑Breton, Mayalen, Castro‑Sepulveda, Mauricio, Simón, Felipe, Cabello-Verrugio, Claudio
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Francisco de Vitoria
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/5559
Acceso en línea:https://hdl.handle.net/10641/5559
Access Level:acceso abierto
Palabra clave:Sarcopenia
Ursodeoxycholic acid
Autophagic flux
Protein synthesis
Bile acids
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spelling Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.Orozco‑Aguilar, JosuéTacchi, FrancoAguirre, FranciscoValero‑Breton, MayalenCastro‑Sepulveda, MauricioSimón, FelipeCabello-Verrugio, ClaudioSarcopeniaUrsodeoxycholic acidAutophagic fluxProtein synthesisBile acidsBackground Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. Methods We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber’s diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. Results UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber’s diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. Conclusions Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.BioMed Central20232023-01-0120232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/5559reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad Francisco de VitoriaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/55592026-06-11T12:44:57Z
dc.title.none.fl_str_mv Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.
title Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.
spellingShingle Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.
Orozco‑Aguilar, Josué
Sarcopenia
Ursodeoxycholic acid
Autophagic flux
Protein synthesis
Bile acids
title_short Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.
title_full Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.
title_fullStr Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.
title_full_unstemmed Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.
title_sort Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.
dc.creator.none.fl_str_mv Orozco‑Aguilar, Josué
Tacchi, Franco
Aguirre, Francisco
Valero‑Breton, Mayalen
Castro‑Sepulveda, Mauricio
Simón, Felipe
Cabello-Verrugio, Claudio
author Orozco‑Aguilar, Josué
author_facet Orozco‑Aguilar, Josué
Tacchi, Franco
Aguirre, Francisco
Valero‑Breton, Mayalen
Castro‑Sepulveda, Mauricio
Simón, Felipe
Cabello-Verrugio, Claudio
author_role author
author2 Tacchi, Franco
Aguirre, Francisco
Valero‑Breton, Mayalen
Castro‑Sepulveda, Mauricio
Simón, Felipe
Cabello-Verrugio, Claudio
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Sarcopenia
Ursodeoxycholic acid
Autophagic flux
Protein synthesis
Bile acids
topic Sarcopenia
Ursodeoxycholic acid
Autophagic flux
Protein synthesis
Bile acids
description Background Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. Methods We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber’s diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. Results UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber’s diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. Conclusions Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10641/5559
url https://hdl.handle.net/10641/5559
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad Francisco de Vitoria
instname_str Universidad Francisco de Vitoria
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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