Role of alcohol metabolism in non-alcoholic steatohepatitis.
Role of alcohol metabolism in non-alcoholic steatohepatitis.
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DOI：
10.1371/journal.pone.0009570
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发表时间：
2010-03-08
期刊：
影响因子：
3.7
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Baker SS;Baker RD;Liu W;Nowak NJ;Zhu L
非酒精性脂肪性肝炎（NASH）是一种严重的非酒精性脂肪性肝病（NAFLD），与肥胖和胰岛素抵抗有关。先前的研究表明，肥胖老鼠的肠道细菌比瘦老鼠产生更多的酒精。为探讨酒精是否参与NASH的发病机制，采用微阵列（NASH, n = 7； NC, n = 4）和实时荧光定量PCR （NASH, n = 6； NC, n = 6）检测NASH患者和正常对照（NC）肝组织中炎症、纤维化和酒精代谢相关基因的表达。与正常肝脏相比，与肝脏炎症和纤维化相关的基因在NASH肝脏中被发现升高。最引人注目的发现是乙醇脱氢酶（ADH）基因、过氧化氢酶和细胞色素P450 2E1基因以及醛脱氢酶基因的基因转录增加。免疫印迹分析证实ADH1和ADH4在NASH肝脏中表达升高（NASH, n = 9； NC, n = 4）。酒精分解代谢途径中所有可用基因的活性增强表明：1)NASH患者血液循环中的酒精浓度升高；2) NASH患者的肝脏优先清除血液循环中的酒精。我们的数据是第一个表明酒精可能导致NAFLD发展的人类证据。
Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD), associated with obesity and insulin resistance. Previous studies suggested that intestinal bacteria produced more alcohol in obese mice than lean animals. To investigate whether alcohol is involved in the pathogenesis of NASH, the expression of inflammation, fibrosis and alcohol metabolism related genes in the liver tissues of NASH patients and normal controls (NCs) were examined by microarray (NASH, n = 7; NC, n = 4) and quantitative real-time PCR (NASH, n = 6; NC, n = 6). Genes related to liver inflammation and fibrosis were found to be elevated in NASH livers compared to normal livers. The most striking finding is the increased gene transcription of alcohol dehydrogenase (ADH) genes, genes for catalase and cytochrome P450 2E1, and aldehyde dehydrogenase genes. Immunoblot analysis confirmed the increased expression of ADH1 and ADH4 in NASH livers (NASH, n = 9; NC, n = 4). The augmented activity of all the available genes of the pathways for alcohol catabolism suggest that 1) alcohol concentration was elevated in the circulation of NASH patients; 2) there was a high priority for the NASH livers to scavenge alcohol from the circulation. Our data is the first human evidence that suggests alcohol may contribute to the development of NAFLD.
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影响因子：
15.9
作者：
Donnelly, KL;Smith, CI;Parks, EJ
通讯作者：
Parks, EJ
影响因子：
6.1
作者：
NELSON, S;BAGBY, G;SUMMER, WR
通讯作者：
SUMMER, WR
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
DOI：
10.1097/01.alc.0000189280.19073.28
发表时间：
2005-11-01
影响因子：
3.2
作者：
Bode, C;Bode, JC
通讯作者：
Bode, JC
影响因子：
4.3
作者：
Kawaratani, Hideto;Tsujimoto, Tatsuhiro;Fukui, Hiroshi
通讯作者：
Fukui, Hiroshi