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采用平行双二级柱-双检测二维全二维气相色谱法对饮食诱导代谢紊乱小鼠进行尿液代谢指纹图谱分析。

Urinary metabolic fingerprinting of mice with diet-induced metabolic derangements by parallel dual secondary column-dual detection two-dimensional comprehensive gas chromatography.

作者信息

Bressanello Davide, Liberto Erica, Collino Massimo, Reichenbach Stephen E, Benetti Elisa, Chiazza Fausto, Bicchi Carlo, Cordero Chiara

机构信息

Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, I-10125 Torino, Italy.

Computer Science and Engineering Department, University of Nebraska, 1400 R Street, Lincoln, NE 68588-0115, USA.

出版信息

J Chromatogr A. 2014 Sep 26;1361:265-76. doi: 10.1016/j.chroma.2014.08.015. Epub 2014 Aug 14.

Abstract

This study investigates the potential of a parallel dual secondary column-dual detection two-dimensional comprehensive GC platform (GC×2GC-MS/FID) for metabolic profiling and fingerprinting of mouse urine. Samples were obtained from a murine model that mimics a typical unhealthy Western diet featuring both high fat and sugar (HFHS) intake, which induces obesity, dyslipidemia, and insulin resistance. Urines collected at different steps of the study were used to obtain pivotal and comparative data on the presence and relative distributions of early markers of metabolic disease. The data elaboration and interpretation work-flow includes an advanced untargeted fingerprinting approach, with peak-region features to locate relevant features to be quantified by external standard calibration. The reliability of untargeted fingerprinting is confirmed by quantitative results on selected relevant features that showed percentages of variations consistent with those observed by comparing raw data quantitative descriptors (2D peak-region volumes and percent of response). Analytes that were up-regulated with % of variation ranging from 30 to 1000, included pyruvic acid, glycerol, fructose, galactose, glucose, lactic acid, mannitol and valine. Down-regulation was evidenced for malonic acid, succinic acid, alanine, glycine, and creatinine. Advanced fingerprinting also is demonstrated for effectively evaluating individual variations during experiments, thus representing a promising tool for personalized intervention studies. In this context, it is interesting to observe that informative features that were not discriminant for the entire population may be relevant for individuals.

摘要

本研究调查了平行双二级柱-双检测二维全二维气相色谱平台(GC×2GC-MS/FID)用于小鼠尿液代谢谱分析和指纹图谱分析的潜力。样本取自一种模拟典型不健康西方饮食(高脂肪和高糖摄入,即HFHS)的小鼠模型,这种饮食会导致肥胖、血脂异常和胰岛素抵抗。在研究的不同阶段收集的尿液用于获取关于代谢疾病早期标志物的存在及相对分布的关键和对比数据。数据处理与解释工作流程包括一种先进的非靶向指纹图谱方法,利用峰区域特征来定位相关特征,以便通过外标校准进行定量。通过对选定相关特征的定量结果证实了非靶向指纹图谱的可靠性,这些结果显示的变化百分比与通过比较原始数据定量描述符(二维峰区域体积和响应百分比)所观察到的一致。上调的分析物,其变化百分比范围为30%至1000%,包括丙酮酸、甘油、果糖、半乳糖、葡萄糖、乳酸、甘露醇和缬氨酸。丙二酸、琥珀酸、丙氨酸、甘氨酸和肌酐则出现下调。先进的指纹图谱还被证明可有效评估实验过程中的个体差异,因此是个性化干预研究的一种有前景的工具。在此背景下,有趣的是观察到对整个人群无鉴别力的信息性特征可能对个体是相关的。

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