title: Influence of dietary fat intake on the endocannabinoid system in lean and obese subjects.
abstract: 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.
authors.affiliation: Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Engeli
authors.forename: Anne-Christin
authors.initials: AC
authors.lastname: Lehmann
authors.forename: Jana
authors.initials: J
authors.lastname: Kaminski
authors.forename: Verena
authors.initials: V
authors.lastname: Haas
authors.forename: Jürgen
authors.initials: J
authors.lastname: Janke
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Zoerner
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000293:Adolescent; D000328:Adult; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D001095:Arachidonic Acids / Q000097:blood; D001786:Blood Glucose; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage*; D015536:Down-Regulation; D063388:Endocannabinoids / Q000097:blood*; D005215:Fasting; D005260:Female; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008994:Monoacylglycerol Lipases / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D013851:Thinness / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D063388:Endocannabinoids; D008071:Lipoprotein Lipase; D008994:Monoacylglycerol Lipases; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D014280:Triglycerides; D000099252:Fatty Acid Amide Hydrolases; C480280:DAGLA protein, human; C078814:anandamide