Influence of dietary fat intake on the endocannabinoid system in lean and obese subjects.

Objective: Endocannabinoid system (ECS) activation promotes obesity-associated metabolic disease. Increased dietary fat intake increases blood endocannabinoids and alters adipose and skeletal muscle ECS gene expression in human.

Methods: Two weeks isocaloric low- (LFD) and high-fat diets (HFD) in obese (n = 12) and normal-weight (n = 17) subjects in a randomized cross-over study were compared. Blood endocannabinoids 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: Baseline fasting plasma endocannabinoids were similar with both diets. Anandamide decreased similarly with high- or low-fat test meals in both groups. Baseline arachidonoylglycerol plasma concentrations were similar between groups and diets, 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 diets had no influence. In contrast, the HFD produced pronounced reductions in skeletal muscle CB1-R and MAGL mRNA expression, whereas obesity did not affect muscular gene expression.

Conclusions: Weight-neutral changes in dietary fat intake cannot explain excessive endocannabinoid availability in human obesity. Obesity and dietary fat intake affect ECS gene expression in a tissue-specific manner.