Lipidomic changes in rat liver after long-term exposure to ethanol.
Lipidomic changes in rat liver after long-term exposure to ethanol.
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DOI：
10.1016/j.taap.2011.05.022
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发表时间：
2011-09-01
影响因子：
3.8
通讯作者：
Ansari, G. A. Shakeel
中科院分区：
文献类型：
--
作者：
Fernando, Harshica;Bhopale, Kamlesh K.;Kondraganti, Shakuntala;Kaphalia, Bhupendra S.;Ansari, G. A. Shakeel
酒精性肝病（ALD）是一种严重的健康问题，发病率和死亡率都很高。在这项研究中，我们研究了乙醇喂养2个月和3个月的大鼠ALD的进展以及脂质组学变化，以了解其机制，并确定可能的生物标志物。雄性Fischer 344大鼠在Lieber-DeCarli饮食中喂食5%乙醇或相当于热量的麦芽糖-糊精。分别于2、3个月末屠宰，取血浆和肝脏。肝脏部分固定用于组织学和免疫组织学研究。采用核磁共振（NMR）技术提取血浆和肝脏脂质。在乙醇喂养大鼠肝脏中观察到一种时间依赖性的脂肪浸润。部分大鼠在3月龄时观察到轻度炎症和氧化应激。从血浆和肝脏中提取的脂肪的质子和磷核磁共振波谱数据的多变量和主成分分析表明，乙醇喂养组与成对喂养组存在分离。乙醇暴露显著增加的肝脂包括脂肪酸和甘油三酯，而磷脂酰胆碱（PC）降低。血浆游离脂肪酸和PC均下降。在肝脏脂质中，脂肪酰基链的不饱和增加，与血浆相反，它减少。我们的研究证实，在乙醇长期暴露下，脂质在酒精诱导的肝脂肪变性中过度积累，并伴有轻度炎症。利用核磁共振脂质组学鉴定的代谢谱可以进一步探索，以建立代表ALD的发病、进展和/或严重程度的生物标志物特征。
Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipid from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plamsa. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD.
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影响因子：
3.7
作者：
Baker SS;Baker RD;Liu W;Nowak NJ;Zhu L
通讯作者：
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LIEBER, CS;SPRITZ, N;DECARLI, LM
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DECARLI, LM
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SCHMID, R
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作者：
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通讯作者：
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