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猪的全代谢系统特征:人类生理学模型

A metabolic system-wide characterisation of the pig: a model for human physiology.

作者信息

Merrifield Claire A, Lewis Marie, Claus Sandrine P, Beckonert Olaf P, Dumas Marc-Emmanuel, Duncker Swantje, Kochhar Sunil, Rezzi Serge, Lindon John C, Bailey Mick, Holmes Elaine, Nicholson Jeremy K

机构信息

Biomolecular Medicine, Department of Surgery and Cancer, Imperial College London, UKSW7 2AZ.

出版信息

Mol Biosyst. 2011 Sep;7(9):2577-88. doi: 10.1039/c1mb05023k. Epub 2011 Jul 14.

DOI:10.1039/c1mb05023k
PMID:21761043
Abstract

The pig is a single-stomached omnivorous mammal and is an important model of human disease and nutrition. As such, it is necessary to establish a metabolic framework from which pathology-based variation can be compared. Here, a combination of one and two-dimensional (1)H and (13)C nuclear magnetic resonance spectroscopy (NMR) and high-resolution magic angle spinning (HR-MAS) NMR was used to provide a systems overview of porcine metabolism via characterisation of the urine, serum, liver and kidney metabolomes. The metabolites observed in each of these biological compartments were found to be qualitatively comparable to the metabolic signature of the same biological matrices in humans and rodents. The data were modelled using a combination of principal components analysis and Venn diagram mapping. Urine represented the most metabolically distinct biological compartment studied, with a relatively greater number of NMR detectable metabolites present, many of which are implicated in gut-microbial co-metabolic processes. The major inter-species differences observed were in the phase II conjugation of extra-genomic metabolites; the pig was observed to conjugate p-cresol, a gut microbial metabolite of tyrosine, with glucuronide rather than sulfate as seen in man. These observations are important to note when considering the translatability of experimental data derived from porcine models.

摘要

猪是单胃杂食性哺乳动物,是人类疾病和营养的重要模型。因此,有必要建立一个代谢框架,以便比较基于病理学的变异。在此,结合一维和二维氢(1H)和碳(13C)核磁共振波谱(NMR)以及高分辨率魔角旋转(HR-MAS)NMR,通过对尿液、血清、肝脏和肾脏代谢组的表征,提供猪代谢的系统概述。发现在这些生物区室中观察到的代谢物在质量上与人类和啮齿动物相同生物基质的代谢特征相当。使用主成分分析和维恩图映射相结合的方法对数据进行建模。尿液代表了所研究的代谢上最独特的生物区室,存在相对较多的可通过NMR检测到的代谢物,其中许多与肠道微生物共代谢过程有关。观察到的主要种间差异在于基因组外代谢物的II期结合;观察到猪将对甲酚(酪氨酸的肠道微生物代谢物)与葡糖醛酸结合,而在人类中则是与硫酸盐结合。在考虑从猪模型获得的实验数据的可转化性时,这些观察结果很重要。

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