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
Biol Res. 2023-03-25; 56(1):
DOI: 10.1186/s40659-023-00426-5

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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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