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PNPLA3表达与患有非酒精性脂肪性肝病的病态肥胖女性的肝脏脂肪变性有关。

PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

作者信息

Aragonès Gemma, Auguet Teresa, Armengol Sandra, Berlanga Alba, Guiu-Jurado Esther, Aguilar Carmen, Martínez Salomé, Sabench Fátima, Porras José Antonio, Ruiz Maikel Daniel, Hernández Mercé, Sirvent Joan Josep, Del Castillo Daniel, Richart Cristóbal

机构信息

Group de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Institut Investigació Sanitària Pere Virgili (IISPV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain.

Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, 43007 Tarragona, Spain.

出版信息

Int J Mol Sci. 2016 Apr 27;17(5):630. doi: 10.3390/ijms17050630.

Abstract

Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

摘要

近期报告表明,含帕他丁样磷脂酶结构域蛋白3(PNPLA3)在非酒精性脂肪性肝病(NAFLD)的病理过程中发挥作用。肝脏中的脂质沉积似乎是NAFLD发病机制中的一个关键过程。本研究的目的是评估肝脏PNPLA3表达、脂质代谢关键基因与病态肥胖女性NAFLD存在情况之间的关联。我们采用实时聚合酶链反应(PCR)分析,对55例病态肥胖受试者肝脏中PNPLA3及脂质代谢相关基因的表达进行分析,这些受试者具有正常肝脏组织学(NL,n = 18)、单纯性脂肪变性(SS,n = 20)和非酒精性脂肪性肝炎(NASH,n = 17)。肝脏活检在减肥手术期间采集。我们观察到,NAFLD患者肝脏中PNPLA3的表达高于NL组。SS组中该表达也高于NL组。有趣的是,我们发现严重SS组中PNPLA3的表达显著高于轻度SS组。此外,转录因子LXRα、PPARα和SREBP2的表达与肝脏中PNPLA3的表达呈正相关。关于rs738409多态性,GG基因型与NASH的存在呈正相关。总之,我们的结果表明,PNPLA3可能与肝脏脂质蓄积有关,主要与单纯性脂肪变性的发生和进展有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/4881456/6336795e5819/ijms-17-00630-g001.jpg

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