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

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

doi:10.1186/s40659-023-00426-5

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

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^*

^*Autor correspondiente de este trabajo

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2 Citas (Scopus)

Resumen

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.

Idioma original	Inglés
Número de artículo	14
Publicación	Biological Research
Volumen	56
N.º	1
DOI	https://doi.org/10.1186/s40659-023-00426-5
Estado	Publicada - 2023

Nota bibliográfica

Funding Information:
C.S. was supported by CONICYT Ph.D. Scholarship Nº 21180609, and “Proyecto de Consolidación de la Internacionalización de la Investigación y Postgrado de la Universidad de Chile, UCH‐1566” (C.S.). R.T. was supported by Agencia Nacional de Investigación y Desarrollo (ANID), Chile: FONDAP 15130011 and FONDECYT 1191078. D. C. was supported by INSERM, Aquitaine Region and French National Research Agency (ANR, ANR-17-CE14-0007 BABrain, ANR-18-CE14-0029 MitObesity, Labex BRAIN ANR-10-LABX-43, ANR-10-EQX-008-1 OPTOPATH). The platform facilities of INSERM U1215 Neurocentre Magendie used for the studies are supported by INSERM, LabEX BRAIN ANR-10-LABX-43 and the University of Bordeaux's IdEx ‘‘Investments for the Future’’ program/GPR BRAIN_2030. Institutional Review Board Statement: The animal study protocol was approved by the Instituto de Nutrición y Tecnología de los Alimentos (Project Identification Code Nº 17,073-INT-UCH).

Funding Information:
We thank Dr. Giovanni Marsicano (INSERM U1215, Bordeaux) for providing the CB1-KO mice, and Samantha Clark (INSERM U1215, Bordeaux) for her technical help. We thank the animal housing, genotyping, transcriptomic and analytical chemistry facilities of INSERM U1215 Neurocentre Magendie, and also for animal caring, genotyping, qPCR studies, and quantification of endocannabinoids.

Publisher Copyright:
© 2023, The Author(s).

Áreas temáticas de ASJC Scopus

Bioquímica, Genética y Biología Molecular General
Ciencias Agrícolas y Biológicas General

ODS de las Naciones Unidas

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Sepúlveda, C., Rodríguez, J. M., Monsalves-Álvarez, M., Donoso-Barraza, C., Pino-de la Fuente, F., Matías, I., Leste-Lasserre, T., Zizzari, P., Morselli, E., Cota, D., Llanos, M., & Troncoso, R. (2023). The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice. Biological Research, 56(1), Artículo 14. https://doi.org/10.1186/s40659-023-00426-5

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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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author = "Carlos Sep{\'u}lveda and Rodr{\'i}guez, {Juan Manuel} and Mat{\'i}as Monsalves-{\'A}lvarez and Camila Donoso-Barraza and {Pino-de la Fuente}, Francisco and Isabelle Mat{\'i}as and Thierry Leste-Lasserre and Philippe Zizzari and Eugenia Morselli and Daniela Cota and Miguel Llanos and Rodrigo Troncoso",

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Sepúlveda, C, Rodríguez, JM, Monsalves-Álvarez, M, Donoso-Barraza, C, Pino-de la Fuente, F, Matías, I, Leste-Lasserre, T, Zizzari, P, Morselli, E, Cota, D, Llanos, M & Troncoso, R 2023, 'The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice', Biological Research, vol. 56, n.º 1, 14. https://doi.org/10.1186/s40659-023-00426-5

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AU - Rodríguez, Juan Manuel

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AU - Donoso-Barraza, Camila

AU - Pino-de la Fuente, Francisco

AU - Matías, Isabelle

AU - Leste-Lasserre, Thierry

AU - Zizzari, Philippe

AU - Morselli, Eugenia

AU - Cota, Daniela

AU - Llanos, Miguel

AU - Troncoso, Rodrigo

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

Resumen

Nota bibliográfica

Áreas temáticas de ASJC Scopus

ODS de las Naciones Unidas

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