The ECS (endocannabinoid system) plays an important role in the onset of obesity and metabolic disorders, implicating central and peripheral mechanisms predominantly via CB1 (cannabinoid type 1) receptors. CB1 receptor antagonist/inverse agonist treatment improves cardiometabolic risk factors and insulin resistance. However, the relative contribution of peripheral organs to the net beneficial metabolic effects remains unclear. In the present study, we have identified the presence of the endocannabinoid signalling machinery in skeletal muscle and also investigated the impact of an HFD (high-fat diet) on lipid-metabolism-related genes and endocannabinoid-related proteins. Finally, we tested whether administration of the CB1 inverse agonist AM251 restored the alterations induced by the HFD. Rats were fed on either an STD (standard/low-fat diet) or an HFD for 10 weeks and then treated with AM251 (3 mg/kg of body weight per day) for 14 days. The accumulated caloric intake was progressively higher in rats fed on the HFD than the STD, resulting in a divergence in body weight gain. AM251 treatment reduced accumulated food/caloric intake and body weight gain, being more marked in rats fed on the HFD. CB2 (cannabinoid type 2) receptor and PPARα (peroxisome-proliferator-activated receptor α) gene expression was decreased in HFD-fed rats, whereas MAGL (monoglyceride lipase) gene expression was up-regulated. These data suggest an altered endocannabinoid signalling as a result of the HFD. AM251 treatment reduced CB2 receptor, PPARγ and AdipoR1 (adiponectin receptor 1) gene expression in STD-fed rats, but only partially normalized the CB2 receptor in HFD-fed rats. Protein levels corroborated gene expression results, but also showed a decrease in DAGL (diacylglycerol) β and DAGLα after AM251 treatment in STD- and HFD-fed rats respectively. In conclusion, the results of the present study indicate a diet-sensitive ECS in skeletal muscle, suggesting that blockade of CB1 receptors could work towards restoration of the metabolic adaption imposed by diet.
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January 2011
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Research Article|
December 15 2010
Expression of the cannabinoid system in muscle: effects of a high-fat diet and CB1 receptor blockade
Ana Crespillo;
Ana Crespillo
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
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Juan Suárez;
Juan Suárez
1
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
†CIBER OBN (Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, 28029 Madrid, Spain
1Correspondence may be addressed to either of these authors (email fernando.rodriguez@fundacionimabis.org or juan.suarez@fundacionimabis.org).
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Francisco J. Bermúdez-Silva;
Francisco J. Bermúdez-Silva
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
†CIBER OBN (Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, 28029 Madrid, Spain
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Patricia Rivera;
Patricia Rivera
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
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Margarita Vida;
Margarita Vida
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
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Monica Alonso;
Monica Alonso
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
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Ana Palomino;
Ana Palomino
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
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Miguel A. Lucena;
Miguel A. Lucena
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
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Antonia Serrano;
Antonia Serrano
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
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Margarita Pérez-Martín;
Margarita Pérez-Martín
‡Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, University of Málaga, 29071 Málaga, Spain
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Manuel Macias;
Manuel Macias
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
†CIBER OBN (Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, 28029 Madrid, Spain
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Pedro Fernández-Llébrez;
Pedro Fernández-Llébrez
‡Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, University of Málaga, 29071 Málaga, Spain
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Fernando Rodríguez de Fonseca
Fernando Rodríguez de Fonseca
1
*Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, 29010 Málaga, Spain
†CIBER OBN (Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, 28029 Madrid, Spain
1Correspondence may be addressed to either of these authors (email fernando.rodriguez@fundacionimabis.org or juan.suarez@fundacionimabis.org).
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Biochem J (2011) 433 (1): 175–185.
Article history
Received:
May 20 2010
Revision Received:
September 29 2010
Accepted:
October 18 2010
Accepted Manuscript online:
October 18 2010
Citation
Ana Crespillo, Juan Suárez, Francisco J. Bermúdez-Silva, Patricia Rivera, Margarita Vida, Monica Alonso, Ana Palomino, Miguel A. Lucena, Antonia Serrano, Margarita Pérez-Martín, Manuel Macias, Pedro Fernández-Llébrez, Fernando Rodríguez de Fonseca; Expression of the cannabinoid system in muscle: effects of a high-fat diet and CB1 receptor blockade. Biochem J 1 January 2011; 433 (1): 175–185. doi: https://doi.org/10.1042/BJ20100751
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