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

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(-2)) and 21 age- and gender-matched lean subjects (BMI: 23.8 +/- 0.4 kg m(-2)) 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 (P < 0.01). Moreover, 2-AG increased in both depots in the obese subjects following weight loss (P < 0.05). 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, P < 0.05) 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. International Journal of Obesity (2011) 35, 1377-1384; doi: 10.1038/ijo.2011.8; published online 15 February 2011