In one study showing chronic FAAH upregulation in the subcutaneous adipose tissue of obese humans, it was suggested that hyperinsulinaemia may cause this upre http://www.selleckchem.com/products/dorsomorphin-2hcl.html gulation, as similarly high FAAH expression was induced in healthy lean humans using the euglycaemic hyperinsulinaemic clamp method. Considering this, we investigated FAAH activity in comparison with fast ing serum levels of insulin and glucose, and HOMA2 % S. In this sample of healthy volunteers, there was no correlation between FAAH activity in subcutaneous adipocytes and fasting serum concentrations of glucose or insulin, or HOMA2 %S, although it should be noted that all subjects had fasting serum levels of these parameters within normal ranges.

In order to investigate further a relationship between insulin or glucose levels and FAAH activity in adipocytes, further studies need to be conducted to include subjects with poor glycaemic control. Serum adipokine levels are known to be dysregulated in obesity, with downregulation of adiponectin and upregulation of leptin and resistin. As yet, few in vivo studies have investigated adipokine levels with regard to the ECS. We found that in healthy humans, FAAH activity in adipocytes is not correlated with fasting serum concentrations of adiponectin, leptin or resistin. It has been shown that a FAAH missense mutation is associated with both lower serum adiponectin concen trations in diabetic patients, and higher serum lep tin levels after weight loss in obese humans, although the systemic nature of the mutation makes it unclear as to the extent of adipocyte involvement in these changes.

In vitro, leptin has been shown to increase FAAH activity in T lymphocytes, although not in neuroblastoma cells, and our results suggest that in vivo leptin does not significantly affect FAAH activity in adipocytes. MGL has a primary role in lipid metabolism, specifi cally in the hydrolysis of monoacylglycerols to release Anacetrapib glycerol and fatty acids that are subsequently trans ported out of the adipocyte. This explains the relatively high activity of MGL compared to FAAH found in mature adipocytes in this study. The effects of MGL activity on 2 AG signalling are substantial, as demonstrated recently in mouse models, showing that both systemic MGL inhibition and MGL gene deletion lead to increased 2 AG levels in the brain and peripheral tissues, and desensitisation of brain CB1 receptors. As MGL is not thought to be under hormonal control in triglyceride catabolism, it has not been exten sively investigated in relation to obesity. However, given the importance of MGL in 2 AG signalling in the ECS, and considering that plasma 2 AG rises with obesity, we investigated whether MGL activity changes with BMI or other markers of adiposity.