Identification of noninvasive biomarkers for alcohol-induced liver disease using urinary metabolomics and the Ppara-null mouse.
Identification of noninvasive biomarkers for alcohol-induced liver disease using urinary metabolomics and the Ppara-null mouse.
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DOI：
10.1021/pr100452b
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发表时间：
2010-08-06
影响因子：
4.4
通讯作者：
Gonzalez FJ
中科院分区：
文献类型：
--
作者：
Manna SK;Patterson AD;Yang Q;Krausz KW;Li H;Idle JR;Fornace AJ Jr;Gonzalez FJ
酒精性肝病（ALD）是美国非事故相关死亡的主要原因。虽然ALD引起的肝损伤在早期发现时是可逆的，但目前的风险评估工具相对不具特异性。识别ALD的早期特异性特征将有助于治疗干预和恢复。在这项研究中，与酒精诱导的肝脏疾病的代谢变化进行了研究，使用酒精喂养的雄性小鼠作为模型的ALD。基于质谱的尿代谢谱的主成分分析表明，酒精处理的野生型和Ppara-null小鼠可以从没有饮酒史信息的对照动物中区分出来。在野生型和Ppara基因敲除小鼠中，乙醇给药期间，硫酸乙酯、乙基-β-D-葡糖苷酸、4-羟基苯乙酸和4-羟基苯乙酸硫酸盐的尿排泄增加，2-羟基苯乙酸、己二酸和庚二酸的尿排泄减少，尽管程度不同。然而，吲哚-3-乳酸是专门升高的酒精暴露在PPara-null小鼠。吲哚-3-乳酸的升高与酒精处理的Ppara基因敲除小鼠中与ALD发展相关的分子事件机械相关。本研究证明了代谢组学方法在Ppara缺失小鼠模型中鉴定ALD发病机制的早期、非侵入性生物标志物的能力。
Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively non-specific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study the metabolic changes associated with alcohol-induced liver disease were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-β-D-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model.
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影响因子：
4.4
作者：
Patterson, Andrew D.;Slanar, Ondrej;Krausz, Kristopher W.;Li, Fei;Hoefer, Constance C.;Perlik, Frantisek;Gonzalez, Frank J.;Idle, Jeffrey R.
通讯作者：
Idle, Jeffrey R.
影响因子：
2.8
作者：
Mancinelli, Rosanna;Ceccanti, Mauro
通讯作者：
Ceccanti, Mauro
影响因子：
2.6
作者：
Naito, Hisao;Yamanoshita, Osamu;Nakajima, Tamie
通讯作者：
Nakajima, Tamie
影响因子：
3.6
作者：
Palmer, CNA;Hsu, MH;Johnson, EF
通讯作者：
Johnson, EF
影响因子：
2.8
作者：
Helander, Anders;Bottcher, Michael;Beck, Olof
通讯作者：
Beck, Olof