Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model.
Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model.
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DOI：
10.1002/oby.21855
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Cherrington NJ
中科院分区：
文献类型：
--
作者：
Han J;Dzierlenga AL;Lu Z;Billheimer DD;Torabzadeh E;Lake AD;Li H;Novak P;Shipkova P;Aranibar N;Robertson D;Reily MD;Lehman-McKeeman LD;Cherrington NJ
特征性的病理变化定义了脂肪变性向非酒精性脂肪性肝炎(NASH)的进展，并与代谢途径相关。NASH的一个常见的啮齿动物模型是蛋氨酸和胆碱缺乏(MCD)饮食。这项研究的目的是对肝脏样本进行全面的代谢分析，以确定在人类条件下哪些途径发生了最明显的变化，并将这些变化与非酒精性脂肪性肝病(NAFLD)的啮齿动物模型进行比较。对测量的所有91种代谢物进行主成分分析表明，与啮齿动物相比，人类的代谢组扰动更大，变化更小。在人类和大鼠NAFLD中，氨基酸和胆汁酸代谢物家族(如天冬氨酸、瓜氨酸、GABA、赖氨酸)的代谢组变化最大；尽管在许多情况下，不同物种之间(胆酸、甜菜碱)的趋势相反。总体而言，这些结果表明，特定途径的代谢产物可能是NASH进展的有用生物标记物，尽管这些标记物可能不对应于啮齿动物NASH模型。在研究NASH的某些终点时，MCD模型可能是有用的；然而，代谢组学结果表明，人类和啮齿动物在疾病的生化发病机制上存在重要差异。
Characteristic pathologic changes define the progression of steatosis to nonalcoholic steatohepatitis (NASH), and are correlated to metabolic pathways. A common rodent model of NASH is the methionine and choline deficient (MCD) diet. The objective of this study was to perform full metabolomic analyses on liver samples to determine which pathways are altered most pronouncedly in the human condition, and to compare these changes to rodent models of nonalcoholic fatty liver disease (NAFLD). A principal components analysis for all 91 metabolites measured indicates that metabolome perturbation is greater and less varied for humans than for rodents. Metabolome changes in human and rat NAFLD were greatest for the amino acid and bile acid metabolite families (e.g. asparagine, citrulline, GABA, lysine); although, in many cases, the trends were reversed when compared between species (cholic acid, betaine). Overall, these results indicate that metabolites of specific pathways may be useful biomarkers for NASH progression, although these markers may not correspond to rodent NASH models. The MCD model may be useful when studying certain endpoints of NASH; however, the metabolomics results indicate important differences between humans and rodents in the biochemical pathogenesis of the disease.
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影响因子：
2.5
作者：
Corbin KD;Zeisel SH
通讯作者：
Zeisel SH
影响因子：
5.6
作者：
Imajo K;Yoneda M;Kessoku T;Ogawa Y;Maeda S;Sumida Y;Hyogo H;Eguchi Y;Wada K;Nakajima A
通讯作者：
Nakajima A
影响因子：
5
作者：
Fisher CD;Lickteig AJ;Augustine LM;Oude Elferink RP;Besselsen DG;Erickson RP;Cherrington NJ
通讯作者：
Cherrington NJ
DOI：
10.1152/ajpregu.00677.2010
发表时间：
2011-12-01
影响因子：
2.8
作者：
Gentile, Christopher L.;Nivala, Angela M.;Maclean, Kenneth N.
通讯作者：
Maclean, Kenneth N.
影响因子：
3.9
作者：
Fisher, Craig D.;Lickteig, Andrew J.;Cherrington, Nathan J.
通讯作者：
Cherrington, Nathan J.