Methods: Two weeks isocaloric low- (LFD) and high-fatdiet (HFD) in obese (n = 12) and normal-weight (n = 17) subjects in a randomized cross-over study were compared. Blood endocannabinoid were measured in the fasting condition and after food intake using mass spectrometry. Adipose and skeletal muscle gene expression was determined using real-time RT-PCR.
Results: Baselinefasting plasma endocannabinoid were similar with both diet. Anandamide decreased similarly with high- or low-fat test meals in both groups. Baseline arachidonoylglycerol plasma concentration were similar between groups and diet, and unresponsive to eating. In subcutaneous adipose tissue, DAGL-α mRNA was upregulated and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mRNAs were down-regulated in obese subjects, but the diet had no influence. In contrast, the HFDproduced pronounced reductions in skeletal muscleCB1-R and MAGL mRNA expression, whereas obesitydid not affect muscular gene expression.
Conclusions: Weight-neutral changes in dietary fat intake cannot explain excessive endocannabinoid availability in humanobesity. Obesity and dietary fat intake affect ECS gene expression in a tissue-specific manner.