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

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 comm...

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Main Authors: Collino, Sebastiano, Martin, François-Pierre J., Montoliu, Ivan, Barger, Jamie L., Da Silva, Laeticia, Prolla, Tomas A., Weindruch, Richard, Kochhar, Sunil
Format: Online
Language:English
Published: MDPI 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937836/
id pubmed-3937836
recordtype oai_dc
spelling pubmed-39378362014-05-27 Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains Collino, Sebastiano Martin, François-Pierre J. Montoliu, Ivan Barger, Jamie L. Da Silva, Laeticia Prolla, Tomas A. Weindruch, Richard Kochhar, Sunil Article 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. MDPI 2013-10-11 /pmc/articles/PMC3937836/ /pubmed/24958256 http://dx.doi.org/10.3390/metabo3040881 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Collino, Sebastiano
Martin, François-Pierre J.
Montoliu, Ivan
Barger, Jamie L.
Da Silva, Laeticia
Prolla, Tomas A.
Weindruch, Richard
Kochhar, Sunil
spellingShingle Collino, Sebastiano
Martin, François-Pierre J.
Montoliu, Ivan
Barger, Jamie L.
Da Silva, Laeticia
Prolla, Tomas A.
Weindruch, Richard
Kochhar, Sunil
Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains
author_facet Collino, Sebastiano
Martin, François-Pierre J.
Montoliu, Ivan
Barger, Jamie L.
Da Silva, Laeticia
Prolla, Tomas A.
Weindruch, Richard
Kochhar, Sunil
author_sort Collino, Sebastiano
title Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains
title_short Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains
title_full Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains
title_fullStr Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains
title_full_unstemmed Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains
title_sort transcriptomics and metabonomics identify essential metabolic signatures in calorie restriction (cr) regulation across multiple mouse strains
description 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.
publisher MDPI
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937836/
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