TY - JOUR A1 - Engeli, Stefan A1 - Lehmann, Anne-Christin A1 - Kaminski, Jana A1 - Haas, Verena A1 - Janke, Urgen A1 - Janke, Jürgen A1 - Zoerner, Alexander A. A1 - Luft, Friedrich C. A1 - Tsikas, Dimitrios A1 - Jordan, Jens T1 - Influence of dietary fat intake on the endocannabinoid system in lean and obese subjects JF - Obesity N2 - 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-alpha 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. Y1 - 2014 U6 - https://doi.org/10.1002/oby.20728 SN - 1930-7381 SN - 1930-739X VL - 22 IS - 5 SP - E70 EP - E76 PB - Wiley-Blackwell CY - Hoboken ER -