Presence of the cannabinoid receptors, CB1 and CB2, in human omental and subcutaneous adipocytes

Roche, Régis; Hoareau, Laurence; Bès-Houtmann, Sandrine; Gonthier, Marie‐Paule; Laborde, Christine; Baron, J. F.; Haffaf, Y; Césari, Maya; Festy, Franck

doi:10.1007/s00418-005-0127-4

Cited by 140 publications

(116 citation statements)

References 43 publications

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“…22 The peripheral effects of the ECS have been studied less than the central effects of the system. 19 Roche et al 13 have established that the CB1 receptor is expressed in both pre-adipocytes and mature adipocytes and in visceral AT (VAT) as well as in subcutaneous AT (SAT), and we have previously shown a lower level of CB1 expression in VAT compared with SAT in lean subjects and similar levels in the two AT depots in obese individuals. 23 CB1 antagonism leads to increased lipolysis in white AT, 24 whereas CB1 stimulation increases glucose uptake in adipocytes.…”

Section: Introductionsupporting

confidence: 51%

“…11 The CB2 is most common in the immune cells, 12 but it is also present in several other tissues including AT. 13 The two most widely studied ECs are 2-AG and AEA, which belongs to different groups of lipids termed as monoacylglycerols and N-acylethanolamines, respectively. 14 The ECs function mainly as neurotransmitters, and because of their highly lipophilic nature, they cannot be stored in vesicles and have to be produced on demand.…”

Section: Introductionmentioning

confidence: 99%

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Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss

et al. 2011

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Context: Endocannabinoids (ECs) have a role in obesity by affecting appetite and through peripheral effects. Obesity is associated with a dysregulation of the endocannabinoid system (ECS). Objective: We aimed to determine the ECS in subcutaneous adipose tissue (AT) in obese subject and investigate the influence of diet-induced weight loss on this system. Design: The obese study participants underwent a 12 weeks diet regimen resulting in 10-12% weight loss. All study participants underwent fasting blood samples and AT biopsies from abdomen and gluteal region, the obese subjects both before and after weight loss. Setting and participants: A total of 21 healthy obese individuals (10 men/11 women, age 39.5 ± 1.6 years, body mass index (BMI): 37.5±0.8 kg m À2 ) and 21 age-and gender-matched lean subjects (BMI: 23.8±0.4 kg m À2 ) were studied. Main outcome measures: The activity of ECS in AT was determined by measuring arachidonoyl glycerol (2-AG) and N-arachidonoylethanolamine/anandamide in AT by mass spectrometry and gene expressions of enzymes and receptors involved in the ECS. Results: The EC, 2-AG was reduced in obese individuals in the gluteal AT depot (Po0.01). Moreover, 2-AG increased in both depots in the obese subjects following weight loss (Po0.05). The gene expression of the CB1 was either not affected by the obese state (in the gluteal AT depot) or reduced (in the abdominal depot, Po0.05) and significantly affected by weight loss. The expression of the degrading enzymes FAAH, FAAH2, MGL and MGL2 was differently affected by obesity, AT depot and weight loss. Conclusion: We found reduced levels of 2-AG in subcutaneous AT in obesity, which increased after weight loss. In abdominal AT, the low CB1 expression was normalised after weight loss, whereas in gluteal AT the CB1 expression was reduced after weight loss. These findings support the concept of a dysregulated ECS in AT in association with obesity.

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Section: Introductionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss

et al. 2011

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“…A detailed investigation of lipogenic enzymes and triglyceride synthesis rates, however, is needed in human adipocytes to clearly establish this role of endocannabinoids. CB 1/2 receptor-mediated changes in intracellular cAMP levels, as recently shown in human adipocytes, may be an important mechanism to influence metabolic enzymes (27). A role of endocannabinoids for adiponectin dysregulation in obesity has been suggested in rodent and human adipocytes (13,14,35).…”

Section: Discussionmentioning

confidence: 88%

“…ing observations led to the discovery of CB 1 receptors first on rodent adipocytes (9,13) and later to the identification of CB 1 receptors on human adipocytes (21,27). Both, the CB 1 Ϫ/Ϫ genotype and rimonabant treatment are associated with a similar gene expression profile in mouse adipose tissue (28).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity

et al. 2006

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The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB 1 ) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects. Circulating 2-arachidonoyl glycerol (2-AG) was significantly correlated with body fat (r ‫؍‬ 0.45, P ‫؍‬ 0.03), visceral fat mass (r ‫؍‬ 0.44, P ‫؍‬ 0.003), and fasting plasma insulin concentrations (r ‫؍‬ 0.41, P ‫؍‬ 0.001) but negatively correlated to glucose infusion rate during clamp (r ‫؍‬ 0.39, P ‫؍‬ 0.009). In visceral adipose tissue, CB 1 mRNA expression was negatively correlated with visceral fat mass (r ‫؍‬ 0.32, P ‫؍‬ 0.01), fasting insulin (r ‫؍‬ 0.48, P < 0.001), and circulating 2-AG (r ‫؍‬ 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r ‫؍‬ 0.39, P ‫؍‬ 0.01) and circulating 2-AG (r ‫؍‬ 0.77, P < 0.001). Our findings suggest that abdominal fat accumulation is a critical correlate of the dysregulation of the peripheral endocannabinoid system in human obesity. Thus, the endocannabinoid system may represent a primary target for the treatment of abdominal obesity and associated metabolic changes. Diabetes 55:3053-3060, 2006 E ndocannabinoids are lipid mediators derived from membrane phospholipids or triglycerides with complex effects on body weight and metabolic regulation (1,2). Several enzymes are involved in the synthesis and degradation of the two most important endocannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG). At least two G-protein-coupled cannabinoid receptors (CB 1 and CB 2 ) have been identified (3,4). Activation of central CB 1 receptors clearly promotes food intake and weight gain (5-7). However, pharmacological blockade with rimonabant (SR141716) or genetic knockout of the CB 1 receptor demonstrated that weight reduction under these conditions is only partly promoted by decreased food intake (8 -10). These findings prompted the search for peripheral metabolic effects of endocannabinoids. CB 1 receptors have now been identified in rodent liver (11), skeletal muscle (12), adipocytes (9,13), and pancreas (14). The potential role of peripheral CB 1 receptors for metabolic regulation is further promoted by statistical analyses of clinical trials, suggesting that the influence of CB 1 receptor blockade on adiponectin levels, lipids, and glucose homeostasis goes beyond the effect of weight loss alone (15-17).In general, endocannabinoid formation and signaling is dependent on external stimuli such as cellular stress, tissue damage, or metabolic challenges (3,4). However, recent findings point to profound changes in the regulation of the endocannabinoid system in obesity. Experimental data suggest that the endocannabinoid sy...

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“…These results may suggest that while differences in food intake could explain long-term enhanced body weight during standard diet feeding, the lack of CB2R protected Cb2 −/− mice from body weight gain during high fat feeding in young animals. Both CB1R and CB2R are present in white adipose tissue [35] and upregulation of CB1R activity in adipose tissue has been associated with increased lipogenesis and decreased lipolysis in obese humans and rodents [9,10,36]. Two-to 4-month-old Cb2 −/− mice presented normal Cnr1 expression in adipose tissue in both the standard and the high-fat feeding condition, suggesting that improved body weight in high fat fed animals was probably not due to decreased CB1R activity.…”

Section: Cb2mentioning

confidence: 95%

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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Presence of the cannabinoid receptors, CB1 and CB2, in human omental and subcutaneous adipocytes

Cited by 140 publications

References 43 publications

Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss

Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss

Dysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity

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

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