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Metabolites 2013, 3(4), 881-911; doi:10.3390/metabo3040881

Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains

1,†,* , 1,†,* , 2, 3
4, 5
1 Nestlé Institute of Health Sciences SA, Molecular Biomarkers Core, Campus EPFL, Quartier de l'innovation, bâtiment H, Lausanne 1015, Switzerland 2 Nestlé Research Center, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland 3 LifeGen Technologies, LLC (Limited Liability Company), Madison, WI 53719, USA 4 Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53704, USA 5 Department of Medicine, University of Wisconsin and William S. Middleton Veteran's Hospital, Madison, WI 53705, USA These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 28 June 2013 / Revised: 23 September 2013 / Accepted: 25 September 2013 / Published: 11 October 2013
(This article belongs to the Special Issue Integrative Metabolomics)
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Calorie restriction (CR) has long been used to study lifespan effects and oppose the development of a broad array of age-related biological and pathological changes (increase healthspan). Yet, a comprehensive comparison of the metabolic phenotype across different genetic backgrounds to identify common metabolic markers affected by CR is still lacking. Using a system biology approach comprising metabonomics and liver transcriptomics we revealed the effect of CR across multiple mouse strains (129S1/SvlmJ, C57BL6/J, C3H/HeJ, CBA/J, DBA/2J, JC3F1/J). Oligonucleotide microarrays identified 76 genes as differentially expressed in all six strains confirmed. These genes were subjected to quantitative RT-PCR analysis in the C57BL/6J mouse strain, and a CR-induced change expression was confirmed for 14 genes. To fully depict the metabolic pathways affected by CR and complement the changes observed through differential gene expression, the metabolome of C57BL6/J was further characterized in liver tissues, urine and plasma levels using a combination or targeted mass spectrometry and proton nuclear magnetic resonance spectroscopy. Overall, our integrated approach commonly confirms that energy metabolism, stress response, lipids regulators and the insulin/IGF-1 are key determinants factors involved in CR regulation.
Keywords: metabolomics; healthy ageing; calorie restriction; lipidomics metabolomics; healthy ageing; calorie restriction; lipidomics
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Collino, S.; Martin, F.-P.J.; Montoliu, I.; Barger, J.L.; Da Silva, L.; Prolla, T.A.; Weindruch, R.; Kochhar, S. Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains. Metabolites 2013, 3, 881-911.

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