Circulating endocannabinoids are differentially modulated during the oral glucose tolerance test

The endocannabinoid system (ECS) is involved in the regulation of food intake and energy expenditure. Increased level of EC lipid mediators anandamide (AEA) and 2-arachydonoylglycerol (2AG) and/or a higher expression of cannabinoid receptor type 1 in central and peripheral districts are supposed to contribute to the development and maintenance of obesity and related dismetabolism. To understand the ECS response to insulin signal and to anthropometric and biochemical parameters, we evaluated the effect of an OGTT on circulating ECs in five fasted obese females (age: 41.4G3.6 years, BMI: 32.5G4.2 kg/m2, waist circumference: 103.4G11.1 cm). Blood samples were collected before and after 30, 60, 90 and 120 min from a 75 g glucose ingestion. Plasma AEA, related Nacylethanolamines palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), 2AG and 1AG were measured by LC–MS/MS. A whole body and specific region composition analysis was performed by dual-energy X-ray absorptiometry. Basal insulin and glucose levels were 9.4G1.1 mU/ml and 91.0G 5.4 mg/dl, and the calculated area under curve (AUC) were 9.777G2.601 and 15 375G4.044 respectively. AEA, PEA, OEA, 2AG and 1AG basal levels were 1.280G0.498, 15.48G3.70, 4.244G1.450, 1.498G0.465 and 0.588G 0.192 pmol/ml respectively. AEA, PEA and OEA significantly decreased along the OGTT (PZ0.004, PZ0.001 and PZ0.003 respectively). At 60 min their level (D(t0Kt60)/t0%) reduced to 0.639G0.340 (51.4%), 9.16G3.69 (41.2%) and 2.276G0.906 pmol/ml (44.9%). Conversely, 2AG and 1AG levels did not significantly change. AEA, PEA and OEA reduction (D(t0Kt60)/t0%) negatively correlated with glucose AUC (rZK0.895, PZ0.040; rZK0.929, PZ0.022; rZK0.948, PZ0.014 respectively) and positively with whole body (rZ0.882, PZ0.048; rZ0.910, PZ0.032; rZ0.944, PZ0.016 respectively) and gynoid lean mass (rZ0.957, PZ0.010; rZ0.967, PZ0.007; rZ0.951, PZ0.013 respectively). No significant correlations were observed for BMI, waist circumference, basal glucose and insulin, insulin AUC and blood lipids. Our preliminary data indicated that N-acylethanolamine levels are suppressed during the OGTT, and that the extent of the suppression is promoted by lean mass and affected by increasing glucose AUC