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Issue 4, 2011
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Metabolomic anatomy of an animal model revealing homeostatic imbalances in dyslipidaemia

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Abstract

Metabolomics is an emerging technology that reveals homeostatic imbalances in biological systems. Global determination of metabolite concentrations in body fluid and tissues provides novel anatomical aspects of pathological conditions that cannot be obtained from target-specific measurements. Here, we characterised metabolic imbalance in Watanabe heritable hyperlipidaemic rabbits as a model of hypercholesterolaemia. Using a mass spectrometry-based system, we measured a total of 335 metabolites in plasma and tissues (liver, aorta, cardiac muscle, and brain) from WHHL and healthy control rabbits. From the comparison between two metabolomic profiles, pathophysiological features including glutathione and phosphatidylcholine metabolism indicated the occurrence of oxidative stress in several tissues. Especially for the liver, imbalanced purine catabolism shed light on the transcriptional activation of xanthine oxidase, which is thought to act in absorbing or possibly triggering oxidative stress. We also applied this system to assess the therapeutic effects of simvastatin administration. After the treatment, a portion of the metabolomic features in pathological conditions showed alterations suggesting restoration of metabolism to the healthy condition. These changes were considered to be due to the pleiotropic action of statin, including antioxidant effects, rather than its main inhibitory action on cholesterol biosynthesis.

Graphical abstract: Metabolomic anatomy of an animal model revealing homeostatic imbalances in dyslipidaemia

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Publication details

The article was received on 02 Aug 2010, accepted on 15 Dec 2010 and first published on 24 Jan 2011


Article type: Paper
DOI: 10.1039/C0MB00141D
Citation: Mol. BioSyst., 2011,7, 1217-1223
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    Metabolomic anatomy of an animal model revealing homeostatic imbalances in dyslipidaemia

    T. Ooga, H. Sato, A. Nagashima, K. Sasaki, M. Tomita, T. Soga and Y. Ohashi, Mol. BioSyst., 2011, 7, 1217
    DOI: 10.1039/C0MB00141D

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