The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice

Abstract The endocannabinoid system (ECS) regulates energy metabolism, has been implicated in the pathogenesis of metabolic diseases and exerts its actions mainly through the type 1 cannabinoid receptor (CB1). Likewise, autophagy is involved in several cellular processes. It is required for the norm...

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Main Authors: Carlos Sepúlveda, Juan Manuel Rodríguez, Matías Monsalves-Álvarez, Camila Donoso-Barraza, Francisco Pino-de la Fuente, Isabelle Matías, Thierry Leste-Lasserre, Philippe Zizzari, Eugenia Morselli, Daniela Cota, Miguel Llanos, Rodrigo Troncoso
Format: Article
Language:English
Published: BMC 2023-03-01
Series:Biological Research
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Online Access:https://doi.org/10.1186/s40659-023-00426-5
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author Carlos Sepúlveda
Juan Manuel Rodríguez
Matías Monsalves-Álvarez
Camila Donoso-Barraza
Francisco Pino-de la Fuente
Isabelle Matías
Thierry Leste-Lasserre
Philippe Zizzari
Eugenia Morselli
Daniela Cota
Miguel Llanos
Rodrigo Troncoso
author_facet Carlos Sepúlveda
Juan Manuel Rodríguez
Matías Monsalves-Álvarez
Camila Donoso-Barraza
Francisco Pino-de la Fuente
Isabelle Matías
Thierry Leste-Lasserre
Philippe Zizzari
Eugenia Morselli
Daniela Cota
Miguel Llanos
Rodrigo Troncoso
author_sort Carlos Sepúlveda
collection DOAJ
description Abstract The endocannabinoid system (ECS) regulates energy metabolism, has been implicated in the pathogenesis of metabolic diseases and exerts its actions mainly through the type 1 cannabinoid receptor (CB1). Likewise, autophagy is involved in several cellular processes. It is required for the normal development of muscle mass and metabolism, and its deregulation is associated with diseases. It is known that the CB1 regulates signaling pathways that control autophagy, however, it is currently unknown whether the ECS could regulate autophagy in the skeletal muscle of obese mice. This study aimed to investigate the role of the CB1 in regulating autophagy in skeletal muscle. We found concomitant deregulation in the ECS and autophagy markers in high-fat diet-induced obesity. In obese CB1-KO mice, the autophagy-associated protein LC3 II does not accumulate when mTOR and AMPK phosphorylation levels do not change. Acute inhibition of the CB1 with JD-5037 decreased LC3 II protein accumulation and autophagic flux. Our results suggest that the CB1 regulates autophagy in the tibialis anterior skeletal muscle in both lean and obese mice.
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spelling doaj.art-8b1746cbb2934b1b94a8b93abd44ac162023-03-26T11:07:03ZengBMCBiological Research0717-62872023-03-0156111210.1186/s40659-023-00426-5The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in miceCarlos Sepúlveda0Juan Manuel Rodríguez1Matías Monsalves-Álvarez2Camila Donoso-Barraza3Francisco Pino-de la Fuente4Isabelle Matías5Thierry Leste-Lasserre6Philippe Zizzari7Eugenia Morselli8Daniela Cota9Miguel Llanos10Rodrigo Troncoso11Laboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de ChileLaboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de ChileUniversidad de O’HigginsLaboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de ChileLaboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de ChileUniversity of Bordeaux, INSERM, Neurocentre Magendie, U1215University of Bordeaux, INSERM, Neurocentre Magendie, U1215University of Bordeaux, INSERM, Neurocentre Magendie, U1215Department of Basic Sciences, Faculty of Medicine and Sciences, Universidad San SebastiánUniversity of Bordeaux, INSERM, Neurocentre Magendie, U1215Laboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de ChileLaboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de ChileAbstract The endocannabinoid system (ECS) regulates energy metabolism, has been implicated in the pathogenesis of metabolic diseases and exerts its actions mainly through the type 1 cannabinoid receptor (CB1). Likewise, autophagy is involved in several cellular processes. It is required for the normal development of muscle mass and metabolism, and its deregulation is associated with diseases. It is known that the CB1 regulates signaling pathways that control autophagy, however, it is currently unknown whether the ECS could regulate autophagy in the skeletal muscle of obese mice. This study aimed to investigate the role of the CB1 in regulating autophagy in skeletal muscle. We found concomitant deregulation in the ECS and autophagy markers in high-fat diet-induced obesity. In obese CB1-KO mice, the autophagy-associated protein LC3 II does not accumulate when mTOR and AMPK phosphorylation levels do not change. Acute inhibition of the CB1 with JD-5037 decreased LC3 II protein accumulation and autophagic flux. Our results suggest that the CB1 regulates autophagy in the tibialis anterior skeletal muscle in both lean and obese mice.https://doi.org/10.1186/s40659-023-00426-5Endocannabinoid receptorSkeletal muscleAutophagyHigh-fat diet
spellingShingle Carlos Sepúlveda
Juan Manuel Rodríguez
Matías Monsalves-Álvarez
Camila Donoso-Barraza
Francisco Pino-de la Fuente
Isabelle Matías
Thierry Leste-Lasserre
Philippe Zizzari
Eugenia Morselli
Daniela Cota
Miguel Llanos
Rodrigo Troncoso
The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
Biological Research
Endocannabinoid receptor
Skeletal muscle
Autophagy
High-fat diet
title The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
title_full The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
title_fullStr The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
title_full_unstemmed The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
title_short The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
title_sort cb1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
topic Endocannabinoid receptor
Skeletal muscle
Autophagy
High-fat diet
url https://doi.org/10.1186/s40659-023-00426-5
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