The expression of receptors for endocannabinoids in human and rodent skeletal muscle

Cavuoto, Paul; McAinch, Andrew J.; Hatzinikolas, George; Janovská, Alena; Game, Philip A.; Wittert, Gary

doi:10.1016/j.bbrc.2007.09.099

Cited by 155 publications

(119 citation statements)

References 42 publications

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“…Anandamide is the most abundant endogenous endocannabinoid and regulates systemic energy metabolism [43]. Anandamide in skeletal muscles participates in the regulation of TRPV1 function [44,45]. We showed that anandamide treatment significantly increased TRPV1 expression (Supplementary information, Figure S6).…”

Section: Discussionmentioning

confidence: 83%

TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

et al. 2011

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Impaired aerobic exercise capacity and skeletal muscle dysfunction are associated with cardiometabolic diseases. Acute administration of capsaicin enhances exercise endurance in rodents, but the long-term effect of dietary capsaicin is unknown. The capsaicin receptor, the transient receptor potential vanilloid 1 (TRPV1) cation channel has been detected in skeletal muscle, the role of which remains unclear. Here we report the function of TRPV1 in cultured C2C12 myocytes and the effect of TRPV1 activation by dietary capsaicin on energy metabolism and exercise endurance of skeletal muscles in mice. In vitro, capsaicin increased cytosolic free calcium and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in C2C12 myotubes through activating TRPV1. In vivo, PGC-1α in skeletal muscle was upregulated by capsaicin-induced TRPV1 activation or genetic overexpression of TRPV1 in mice. TRPV1 activation increased the expression of genes involved in fatty acid oxidation and mitochondrial respiration, promoted mitochondrial biogenesis, increased oxidative fibers, enhanced exercise endurance and prevented high-fat diet-induced metabolic disorders. Importantly, these effects of capsaicin were absent in TRPV1-deficient mice. We conclude that TRPV1 activation by dietary capsaicin improves energy metabolism and exercise endurance by upregulating PGC-1α in skeletal muscles. The present results indicate a novel therapeutic strategy for managing metabolic diseases and improving exercise endurance.

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Section: Discussionmentioning

confidence: 83%

TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

et al. 2011

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“…In both mice and humans, CB2R is also present in the main peripheral organs responsible for the control of metabolism, including the liver [18], adipose tissue [5,[19][20][21], skeletal muscle [22] and pancreatic islets [23]. Obesity leads to increased expression of the cannabinoid receptor 2 gene (Cb2 [also known as Cnr2]) both in adipose tissue and liver in high fat fed and ob/ob mice [24].…”

Section: Introductionmentioning

confidence: 99%

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

et al. 2010

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Aims/hypothesis The endocannabinoid system has a key role in energy storage and metabolic disorders. The endocannabinoid receptor 2 (CB2R), which was first detected in immune cells, is present in the main peripheral organs responsible for metabolic control. During obesity, CB2R is involved in the development of adipose tissue inflammation and fatty liver. We examined the long-term effects of CB2R deficiency in glucose metabolism. Methods Mice deficient in CB2R (Cb2 −/− [also known as Cnr2]) were studied at different ages (2-12 months). Twomonth-old Cb2 −/− and wild-type mice were treated with a selective CB2R antagonist or fed a high-fat diet.Results The lack of CB2R in Cb2 −/− mice led to greater increases in food intake and body weight with age than in Cb2 +/+ mice. However, 12-month-old obese Cb2 −/− mice did not develop insulin resistance and showed enhanced insulin-stimulated glucose uptake in skeletal muscle. In agreement, adipose tissue hypertrophy was not associated with inflammation. Similarly, treatment of wild-type mice with CB2R antagonist resulted in improved insulin sensitivity. Moreover, when 2-month-old Cb2 −/− mice were fed a high-fat diet, reduced body weight gain and normal insulin sensitivity were observed. Conclusions/interpretation These results indicate that the lack of CB2R-mediated responses protected mice from both age-related and diet-induced insulin resistance, suggesting that these receptors may be a potential therapeutic target in obesity and insulin resistance.

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“…Besides the CNS, CB1Rs are also widely expressed in tissues outside the CNS, such as liver, adipose tissue, skeletal muscle and the pancreas [7][8][9][10][11]. There is evidence that several therapeutic benefits of CB1R antagonists are mediated by their interaction with CB1R in peripheral tissues outside the CNS and that many of their effects are independent of effects on appetite and changes in body weight.…”

Section: Introductionmentioning

confidence: 99%

Acute cannabinoid receptor type 1 (CB1R) modulation influences insulin sensitivity by an effect outside the central nervous system in mice

et al. 2011

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Aims/hypothesis Modulation of central nervous system (CNS) and extra-CNS cannabinoid receptor type 1 (CB1R) affects metabolic conditions, independently of weight loss. Here we examined the relative contributions of acute CNS and extra-CNS CB1R modulation on insulin sensitivity using pharmacological gain-and loss-of-function of CB1R in mice. Methods We assessed the effects of acute modulation of CB1R on insulin sensitivity and tissue glucose uptake by administering a CB1R agonist (HU210) and antagonist (AM251) (vs vehicle) i.v. in wild-type mice. In addition, we administered a CB1R agonist (vs vehicle) systemically (i.v.) to Cb1r (also known as Cnr1) knockout (Cb1r −/− ) mice or intracerebroventricularly (i.c.v.) in wild-type mice to elucidate the peripheral vs CNS-mediated regulatory effect of CB1R on insulin sensitivity.Results HU210 induced significant insulin resistance in wild-type mice with a reduction of whole-body glucose disappearance rate and muscle Akt phosphorylation, as well as of glucose uptake by skeletal muscle, but not by adipose tissue, changes that were prevented by pretreatment with AM251. HU210 did not affect insulin sensitivity in Cb1r −/− mice, suggesting that the observed effects were mediated through CB1R. HU210 administered i.c.v. did not induce insulin resistance, suggesting that acute stimulation of CNS CB1R was not required for this effect. Conclusions/interpretation Skeletal muscle insulin sensitivity is affected by acute CB1R modulation. These changes are mediated by extra-CNS CB1R, probably by the receptors in skeletal muscle tissue.

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The expression of receptors for endocannabinoids in human and rodent skeletal muscle

Cited by 155 publications

References 42 publications

TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age

Acute cannabinoid receptor type 1 (CB1R) modulation influences insulin sensitivity by an effect outside the central nervous system in mice

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