Serum levels of endocannabinoids are independently associated with nonalcoholic fatty liver disease

• Published in: Obesity (Silver Spring, Md.) Md.), 2017-01, Vol.25 (1), p.94-101
• Main Authors: Zelber‐Sagi, Shira, Azar, Shahar, Nemirovski, Alina, Webb, Muriel, Halpern, Zamir, Shibolet, Oren, Tam, Joseph
• Format: Article
• Language: English
• Subjects: Adult; Alanine Transaminase - blood; Alcohol; Arachidonic Acids - blood; Biopsy; Body mass index; Case-Control Studies; Clinical trials; Endocannabinoids - blood; Enzymes; Family medical history; Fasting; Female; Glycerides - blood; Humans; Liver diseases; Magnetic Resonance Imaging; Male; Metabolism; Middle Aged; Mortality; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - diagnostic imaging; Non-alcoholic Fatty Liver Disease - metabolism; Obesity; Obesity - blood; Polyunsaturated Alkamides - blood; Rodents; Studies; Ultrasonic imaging; Waist Circumference
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.21687

Objective To evaluate the association between circulating levels of endocannabinoids (eCBs) and non‐alcoholic fatty liver disease (NAFLD). Methods 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. Results 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. Conclusions 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.