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 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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Main Authors: Sepúlveda,Carlos, Rodríguez,Juan Manuel, Monsalves-Álvarez,Matías, Donoso-Barraza,Camila, Pino-de la Fuente,Francisco, Matías,Isabelle, Leste-Lasserre,Thierry, Zizzari,Philippe, Morselli,Eugenia, Cota,Daniela, Llanos,Miguel, Troncoso,Rodrigo
Format: Digital revista
Language:English
Published: Sociedad de Biología de Chile 2023
Online Access:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602023000100214
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spelling oai:scielo:S0716-976020230001002142023-04-16The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in miceSepúlveda,CarlosRodríguez,Juan ManuelMonsalves-Álvarez,MatíasDonoso-Barraza,CamilaPino-de la Fuente,FranciscoMatías,IsabelleLeste-Lasserre,ThierryZizzari,PhilippeMorselli,EugeniaCota,DanielaLlanos,MiguelTroncoso,Rodrigo Endocannabinoid receptor Skeletal muscle Autophagy High-fat diet 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.56 20232023-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602023000100214en10.1186/s40659-023-00426-5
institution SCIELO
collection OJS
country Chile
countrycode CL
component Revista
access En linea
databasecode rev-scielo-cl
tag revista
region America del Sur
libraryname SciELO
language English
format Digital
author Sepúlveda,Carlos
Rodríguez,Juan Manuel
Monsalves-Álvarez,Matías
Donoso-Barraza,Camila
Pino-de la Fuente,Francisco
Matías,Isabelle
Leste-Lasserre,Thierry
Zizzari,Philippe
Morselli,Eugenia
Cota,Daniela
Llanos,Miguel
Troncoso,Rodrigo
spellingShingle Sepúlveda,Carlos
Rodríguez,Juan Manuel
Monsalves-Álvarez,Matías
Donoso-Barraza,Camila
Pino-de la Fuente,Francisco
Matías,Isabelle
Leste-Lasserre,Thierry
Zizzari,Philippe
Morselli,Eugenia
Cota,Daniela
Llanos,Miguel
Troncoso,Rodrigo
The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
author_facet Sepúlveda,Carlos
Rodríguez,Juan Manuel
Monsalves-Álvarez,Matías
Donoso-Barraza,Camila
Pino-de la Fuente,Francisco
Matías,Isabelle
Leste-Lasserre,Thierry
Zizzari,Philippe
Morselli,Eugenia
Cota,Daniela
Llanos,Miguel
Troncoso,Rodrigo
author_sort Sepúlveda,Carlos
title 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_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_sort cb1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice
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.
publisher Sociedad de Biología de Chile
publishDate 2023
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602023000100214
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