This study investigated whether there was a depot difference in abdominal and gluteal subcutaneous adipose tissue gene expression of two important components of the endocannabinoid system, CB1 and FAAH, and whether caloric restriction alone, and caloric restriction plus aerobic exercise differentially influenced adipose tissue CB1 and FAAH gene expression in obese older women. Our findings showed that compared to gluteal adipose tissue, abdominal adipose tissue had higher FAAH gene expression. Caloric restriction alone lowered gluteal CB1 and FAAH gene expression, whereas caloric restriction plus aerobic exercise reduced abdominal adipose tissue FAAH gene expression.
Previous studies indicate that circulating levels of endocannabinoids are elevated in obesity, possibly reflecting a partial overflow from the tissues that produce and release endocannabinoids . Adipose tissue expresses all the essential components of the endocannabinoid system, therefore is possible the main organ that contributes to the elevated circulating endocannabinoid levels and metabolic dysfunctions . The increased adipose tissue endocannabinoid levels could be due to an increased production and/or a decreased degradation. Several human studies reported that CB1 and FAAH gene expression in visceral and subcutaneous adipose tissue were decreased with obesity and the expression levels were negatively related to visceral fatness [7, 10, 23]. However, other studies reported no changes in CB1 gene expression in visceral and subcutaneous adipose tissue , or even elevated CB1 and FAAH gene expression in visceral and subcutaneous adipose tissue with obesity [24, 25]. Two recent studies indicated that CB1 gene expression in visceral adipose tissue was positively related to visceral fat mass in obese-hypertensive patients , and FAAH activity in subcutaneous adipose tissue correlated positively to BMI in healthy adults . All these studies were cross-sectional comparison studies.
Several previous human studies compared the depot differences in adipose tissue CB1 and FAAH gene expression. Interestingly, some studies indicate that visceral adipose tissue expresses higher levels of CB1 and FAAH than subcutaneous adipose tissue in obese individuals [10, 11]. In one study, although obese subjects had lower expression of CB1 and FAAH in both subcutaneous and visceral adipose tissue than lean subjects, CB1 and FAAH expression levels in visceral adipose tissue are higher than those in subcutaneous adipose tissue in all three groups, including lean, subcutaneous obese and visceral obese individuals . A recent study reported that there were depot differences in subcutaneous adipose tissue CB1 gene expression levels in obese individuals . Here, our findings support that there are depot differences in upper and lower body subcutaneous adipose tissue FAAH gene expression in obese women. The differences in FAAH expression among different adipose tissue depots could be due to the differences in endocannabinoid levels in these depots, which are influenced by adipose tissue inflammatory cytokines.
There are limited data regarding the effects of weigh loss and/or exercise training on adipose tissue endocannabinoid system in obesity. In two previous studies, weight loss by 5% did not change abdominal adipose tissue CB1 and FAAH gene expression [7, 13]. Weight loss also did not influence circulating levels of endocannabinoids [7, 13]. In a recent study, dietary weight loss by 10-12% altered subcutaneous adipose tissue 2-AG levels and lowered CB1 and FAAH gene expression levels in gluteal, but not abdominal adipose tissue . The possible reason for the mixed results could be the differences in the amounts of weight loss in these studies. In an animal study, high-fat feeding significantly increased visceral and subcutaneous adipose tissue CB1 protein expression and exercise training inhibited this high-fat feeding related effects on adipose tissue CB1 protein expression . However, there were no human studies regarding the effects of exercise training on adipose tissue endocannabinoid system.
In the current study, we observed that caloric restriction lowered gluteal adipose tissue CB1 and FAAH gene expression. These results support the findings of another study  and may indicate that weight loss by more than 10% may alter adipose tissue endocannabinoid-related gene expression. Moreover, caloric restriction plus exercise training, including moderate- and vigorous-intensity aerobic exercise, lowered abdominal adipose tissue FAAH gene expression. In a previous study, abdominal adipose tissue FAAH gene expression is positively related to hyerinsulinemia . Moreover, visceral adipose tissue endocannabinoid system activation was mediated by inflammatory cytokines in obesity . In the current study, changes in endocannabinoid system gene expression tended to be related to changes in IL-6 and TNF-α gene expression, indicating a possible link between endocannabinoid system and chronic inflammation in obese individual under diet and exercise interventions.
The findings that abdominal adipose tissue expresses higher levels of FAAH than gluteal adipose tissue, and caloric restriction and caloric restriction plus exercise differentially influenced local adipose tissue endocannabinoid system are interesting. It is notable that circulating and adipose tissue levels of AEA and 2-AG were not measured. Addition of these measures in future studies will provide us with a clearer picture of the depot differences and intervention effects on adipose tissue endocannabinoid system. One of the limitations of the current study is that the sample size in each group was relatively small. With bigger sample size, we would be able to detect a significant exercise effect on abdominal adipose tissue FAAH gene expression in obese individuals under caloric restriction.