Zelber-Sagi Shira, Azar Shahar, Nemirovski Alina, Webb Muriel, Halpern Zamir, Shibolet Oren, Tam Joseph
Department of Gastroenterology, Liver Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
School of Public Health, University of Haifa, Haifa, Israel.
Obesity (Silver Spring). 2017 Jan;25(1):94-101. doi: 10.1002/oby.21687. Epub 2016 Nov 15.
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.
评估内源性大麻素（eCBs）循环水平与非酒精性脂肪性肝病（NAFLD）之间的关联。
采用液相色谱/串联质谱法分析了105名接受NAFLD筛查的志愿者血清中主要的eCBs、花生四烯乙醇胺（AEA）和2-花生四烯酸甘油酯（2-AG）及其内源性前体和分解产物花生四烯酸（AA）的水平。评估了肝脏超声、空腹血液检查和人体测量数据。通过肝肾超声指数（代表肝脏与肾脏亮度水平之比）对肝脏脂肪进行定量。
NAFLD患者的AA水平（pmol/mL）（2721±1112 vs. 2248±977，P = 0.022）和2-AG水平（46.5±25.8 vs. 33.5±13.6，P = 0.003）较高，但AEA水平无差异。在男性和女性以及超重和肥胖亚组中均观察到NAFLD患者中AA和2-AG水平较高的趋势。在对年龄、性别和BMI（OR = 1.001，1.000 - 1.001 95% CI，P = 0.008；OR = 1.05，1.01 - 1.09，P = 0.006）或腰围进行调整后，AA和2-AG与NAFLD的关联仍然存在。
本研究首次表明，与对照组相比，NAFLD患者中2-AG和AA的循环水平较高，且与肥胖无关。这些发现可能提示eCBs在NAFLD发病机制中具有独立作用。
