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斑马鱼(Danio rerio)酒精性脂肪肝的代谢谱分析。

Metabolic profiling of an alcoholic fatty liver in zebrafish (Danio rerio).

作者信息

Jang Zi-Hey, Chung Hee-Chung, Ahn Yun Gyong, Kwon Yong-Kook, Kim Jin-Sup, Ryu Jae-Ho, Ryu Do Hyun, Kim Cheol-Hee, Hwang Geum-Sook

机构信息

Seoul Centre, Korea Basic Science Institute, Seoul 136-713, Republic of Korea.

出版信息

Mol Biosyst. 2012 Jul 6;8(7):2001-9. doi: 10.1039/c2mb25073j. Epub 2012 Apr 25.

DOI:10.1039/c2mb25073j
PMID:22532405
Abstract

Zebrafish (Danio rerio) is becoming a popular developmental biology model to study diseases and for drug discovery. In this study, we performed proton nuclear magnetic resonance spectroscopy ((1)H-NMR)- and gas chromatography-mass spectrometry (GC/MS)-based metabolic profiling of an alcoholic fatty liver using a zebrafish disease model. We examined metabolic differences between the control and alcoholic fatty liver groups in zebrafish to determine how metabolism in an alcoholic fatty liver is regulated. Multivariate statistical analysis showed a significant difference between the control and alcoholic fatty liver groups. The alcoholic fatty liver group showed increased excretion of isoleucine, acetate, succinate, choline, creatine, acetoacetate, 3-hydroxybutyrate (3HB), ethyl glucuronide (EtG), lactate/pyruvate ratio, fatty acids, and cholesterol, and decreased excretion of citrate, aspartate, tyrosine, glycine, glucose, alanine, betaine, and maltose. Metabolites identified in the fatty liver groups were associated with long-term alcohol consumption, which causes both oxidation-reduction (redox) changes and oxidative stress. This study suggests that global metabolite profiling in a zebrafish model can provide insights into the metabolic changes in an alcoholic fatty liver.

摘要

斑马鱼(Danio rerio)正成为一种用于研究疾病和药物发现的热门发育生物学模型。在本研究中,我们使用斑马鱼疾病模型对酒精性脂肪肝进行了基于质子核磁共振波谱法((1)H-NMR)和气相色谱-质谱联用(GC/MS)的代谢谱分析。我们研究了斑马鱼对照组和酒精性脂肪肝组之间的代谢差异,以确定酒精性脂肪肝中的代谢是如何被调节的。多变量统计分析显示对照组和酒精性脂肪肝组之间存在显著差异。酒精性脂肪肝组中异亮氨酸、乙酸盐、琥珀酸盐、胆碱、肌酸、乙酰乙酸、3-羟基丁酸(3HB)、葡萄糖醛酸乙酯(EtG)、乳酸/丙酮酸比值、脂肪酸和胆固醇的排泄增加,而柠檬酸盐、天冬氨酸、酪氨酸、甘氨酸、葡萄糖、丙氨酸、甜菜碱和麦芽糖的排泄减少。在脂肪肝组中鉴定出的代谢物与长期饮酒有关,长期饮酒会导致氧化还原(redox)变化和氧化应激。本研究表明,斑马鱼模型中的整体代谢物谱分析可以为酒精性脂肪肝的代谢变化提供见解。

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