title: Serum levels of endocannabinoids are independently associated with nonalcoholic fatty liver disease.
abstract: To evaluate the association between circulating levels of endocannabinoids (eCBs) and non-alcoholic fatty liver disease (NAFLD).
  
  
  
  The serum levels of the main eCBs, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their endogenous precursor and breakdown product, arachidonic acid (AA), were analyzed by liquid chromatography/tandem mass spectrometry in 105 volunteers screened for NAFLD. Hepatic ultrasound, fasting blood tests, and anthropometrics were assessed. Liver fat was quantified by the hepato-renal-ultrasound index representing the ratio between the brightness level of the liver and the kidney.
  
  
  
  Patients with NAFLD had higher levels (pmol/mL) of AA (2,721 ± 1,112 vs. 2,248 ± 977, P = 0.022) and 2-AG (46.5 ± 25.8 vs. 33.5 ± 13.6, P = 0.003), but not AEA. The trend for higher levels of AA and 2-AG in the presence of NAFLD was observed in both genders and within subgroups of overweight and obesity. The association of AA and 2-AG with NAFLD was maintained with adjustment for age, gender, and BMI (OR = 1.001, 1.000-1.001 95% CI, P = 0.008 and OR = 1.05, 1.01-1.09, P = 0.006, respectively) or waist circumference.
  
  
  
  This study is the first to show high circulating levels of 2-AG and AA in NAFLD patients compared with controls, independent of obesity. The findings may suggest an independent role of eCBs in the pathogenesis of NAFLD.
authors.affiliation: Department of Gastroenterology, Liver Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.|School of Public Health, University of Haifa, Haifa, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Zelber-Sagi
authors.affiliation: Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Shahar
authors.initials: S
authors.lastname: Azar
authors.affiliation: Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Nemirovski
authors.affiliation: Department of Gastroenterology, Liver Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.|The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Muriel
authors.initials: M
authors.lastname: Webb
authors.affiliation: Department of Gastroenterology, Liver Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.|The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
authors.affiliation: Department of Gastroenterology, Liver Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.|The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Shibolet
authors.affiliation: Obesity and Metabolism Laboratory, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Tam
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001095:Arachidonic Acids / Q000097:blood; D016022:Case-Control Studies; D063388:Endocannabinoids / Q000097:blood*; D005260:Female; D005989:Glycerides / Q000097:blood; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009765:Obesity / Q000097:blood; D053284:Polyunsaturated Alkamides / Q000097:blood; D055105:Waist Circumference
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; D000410:Alanine Transaminase; C078814:anandamide