Auguet Teresa, Berlanga Alba, Guiu-Jurado Esther, Terra Ximena, Martinez Salomé, Aguilar Carmen, Filiu Elisa, Alibalic Ajla, Sabench Fàtima, Hernández Mercé, Del Castillo Daniel, Richart Cristóbal
Grup GEMMAIR (AGAUR) and Grup de Recerca en Medicina Aplicada, Departament de Medicina i Cirurgia, IISPV, Hospital Universitari Joan XXIII, Universitat Rovira i Virgili (URV), Mallafré Guasch 4, Catalonia, 43007 Tarragona, Spain ; Servei Medicina Interna, Department of Internal Medicine, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili, Mallafré Guasch 4, Catalonia, 43007 Tarragona, Spain.
Grup GEMMAIR (AGAUR) and Grup de Recerca en Medicina Aplicada, Departament de Medicina i Cirurgia, IISPV, Hospital Universitari Joan XXIII, Universitat Rovira i Virgili (URV), Mallafré Guasch 4, Catalonia, 43007 Tarragona, Spain.
Biomed Res Int. 2014;2014:502542. doi: 10.1155/2014/502542. Epub 2014 Apr 23.
Recent reports suggest a role for the endocannabinoid system in the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between liver expression of cannabinoid (CB) receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different histological stages of NAFLD.
We analysed hepatic CB1 and CB2 mRNA expression, and the expression of genes involved in lipid metabolism in 72 MO women, subclassified by liver histology into MO with normal liver (NL, n = 16), simple steatosis (SS, n = 28), and nonalcoholic steatohepatitis (NASH, n = 28) by enzyme-linked immunosorbent assay and RT-PCR.
We found that CB1 mRNA expression was significantly higher in NASH compared with SS and correlated negatively with PPARα. Regarding CB2, CB2 mRNA expression correlated positively with ACC1, PPARγ, IL6, TNFα, resistin, and adiponectin.
The increased expression of CB1 in NASH and the negative correlation with PPARα suggest a deleterious role of CB1 in NAFLD. Regarding CB2, its positive correlation with the anti-inflammatory molecule adiponectin and, paradoxically, with inflammatory genes suggests that this receptor has a dual role. Taken together, our results suggest that endocannabinoid receptors might be involved in the pathogenesis of NAFLD, a finding which justifies further study.
近期报告表明内源性大麻素系统在非酒精性脂肪性肝病（NAFLD）的病理过程中发挥作用。本研究旨在调查患有不同组织学阶段NAFLD的病态肥胖（MO）女性肝脏中大麻素（CB）受体亚型CB1和CB2的表达之间的关系。
我们通过酶联免疫吸附测定和逆转录聚合酶链反应分析了72名MO女性的肝脏CB1和CB2 mRNA表达以及参与脂质代谢的基因表达，这些女性根据肝脏组织学分为肝脏正常的MO（NL，n = 16）、单纯性脂肪变性（SS，n = 28）和非酒精性脂肪性肝炎（NASH，n = 28）。
我们发现，与SS相比，NASH中CB1 mRNA表达显著更高，且与PPARα呈负相关。关于CB2，CB2 mRNA表达与ACC1、PPARγ、IL6、TNFα、抵抗素和脂联素呈正相关。
NASH中CB1表达增加以及与PPARα的负相关表明CB1在NAFLD中起有害作用。关于CB2，其与抗炎分子脂联素以及矛盾地与炎症基因的正相关表明该受体具有双重作用。综上所述，我们的结果表明内源性大麻素受体可能参与NAFLD的发病机制，这一发现值得进一步研究。
