Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study
Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study
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DOI：
10.1194/jlr.m017368
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发表时间：
2011-11-01
影响因子：
6.5
通讯作者：
Blaner, William S.
中科院分区：
文献类型：
--
作者：
Clugston, Robin D.;Jiang, Hongfeng;Blaner, William S.
长期饮酒与哺乳动物脂肪肝有关。本研究的目的是使用靶向脂质组学方法了解酒精喂养的C57 BL/6小鼠的脂质代谢失调。液相色谱串联质谱法用于分析几种脂质类，包括游离脂肪酸，脂肪酰辅酶A，脂肪酸乙酯，鞘脂，神经酰胺，和内源性大麻素，在血浆和肝脏样品从控制和酒精喂养的小鼠。脂质组学数据的解释增加了重要的代谢酶在脂质途径研究的基因表达分析。酒精喂养与i）分别与线粒体脂肪酸氧化减少和脂肪酰辅酶A合成减少相关的肝游离脂肪酸水平增加和脂肪酰辅酶A水平降低; ii）与前体分子鞘氨醇和鞘氨醇水平升高相关的肝神经酰胺水平增加;和iii）内源性大麻素anandamide的肝水平增加，与其分解代谢酶脂肪酸酰胺水解酶的表达降低有关。脂质组学和基因表达分析的独特组合允许更好地了解酒精性脂肪肝疾病发展中脂质代谢失调的机制。克拉格斯顿河D、H. Jiang，M. X.利河，巴西-地Piantedosi，J. J. Yuen，R. Ramakrishnan，M. J.刘易斯，M. E. Gottesman，L-S。黄岛，澳-地J·戈德堡警局Berk和W. S.布兰纳C57 BL/6小鼠酒精喂养后肝脏脂质代谢改变：靶向脂质组学和基因表达研究J. Lipid Res. 2011. 52：2021-2031。
Chronic alcohol consumption is associated with fatty liver disease in mammals. The object of this study was to gain an understanding of dysregulated lipid metabolism in alcohol-fed C57BL/6 mice using a targeted lipidomic approach. Liquid chromatography tandem mass spectrometry was used to analyze several lipid classes, including free fatty acids, fatty acyl-CoAs, fatty acid ethyl esters, sphingolipids, ceramides, and endocannabinoids, in plasma and liver samples from control and alcohol-fed mice. The interpretation of lipidomic data was augmented by gene expression analyses for important metabolic enzymes in the lipid pathways studied. Alcohol feeding was associated with i) increased hepatic free fatty acid levels and decreased fatty acyl-CoA levels associated with decreased mitochondrial fatty acid oxidation and decreased fatty acyl-CoA synthesis, respectively; ii) increased hepatic ceramide levels associated with higher levels of the precursor molecules sphingosine and sphinganine; and iii) increased hepatic levels of the endocannabinoid anandamide associated with decreased expression of its catabolic enzyme fatty acid amide hydrolase. The unique combination of lipidomic and gene expression analyses allows for a better mechanistic understanding of dysregulated lipid metabolism in the development of alcoholic fatty liver disease.-Clugston, R. D., H. Jiang, M. X. Lee, R. Piantedosi, J. J. Yuen, R. Ramakrishnan, M. J. Lewis, M. E. Gottesman, L-S. Huang, I. J. Goldberg, P. D. Berk, and W. S. Blaner. Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study. J. Lipid Res. 2011. 52: 2021-2031.