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


  • S. Engeli
  • A.C. Lehmann
  • J. Kaminski
  • V. Haas
  • J. Janke
  • A.A. Zoerner
  • F.C. Luft
  • D. Tsikas
  • J. Jordan


  • Obesity


  • Obesity 22 (5): E70-E76


  • Objective: Endocannabinoid system activation promotes obesity-associated metabolic disease. We hypothesized that increased dietary fat intake increases blood endocannabinoids and alters adipose and skeletal muscle endocannabinoid system gene expression in man. Design and Methods: We compared two weeks isocaloric low and high-fat diets in obese (n=12) and normal-weight (n=17) subjects in a randomized cross-over study. Blood endocannabinoids were measured in the fasting condition and after food intake by mass spectrometry. Adipose and skeletal muscle gene expression was determined by 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 up-regulated and FAAH and MAGL mRNAs were down-regulated in obese subjects, but the diets had no influence. In contrast, the high-fat diet 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 endocannabinoid system gene expression in a tissue-specific manner.