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Metabolites 2012, 2(2), 366-381; doi:10.3390/metabo2020366
Article

Metabolomic and Lipidomic Analysis of the Heart of Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-β Knock Out Mice on a High Fat Diet

1, 2, 3, 2 and 1,4,*
1 Department of Biochemistry, 80 Tennis Court Road, University of Cambridge, Cambridge, CB2 1GA, UK 2 Metabolic Research Laboratories, Level 4, Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK 3 Department of Biosciences, CV/GI iMED, AstraZeneca R&D, Mölndal, S-43183, Sweden 4 Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, 120 Fulbourn Road, Cambridge, CB1 9NL, UK
* Author to whom correspondence should be addressed.
Received: 5 April 2012 / Revised: 21 May 2012 / Accepted: 4 June 2012 / Published: 18 June 2012
(This article belongs to the Special Issue Lipidomics)
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Abstract

The peroxisome proliferator-activated receptor-γ coactivators (PGC-1) are transcriptional coactivators with an important role in mitochondrial biogenesis and regulation of genes involved in the electron transport chain and oxidative phosphorylation in oxidative tissues including cardiac tissue. These coactivators are thought to play a key role in the development of obesity, type 2 diabetes and the metabolic syndrome. In this study we have used a combined metabolomic and lipidomic analysis of cardiac tissue from the PGC-1β null mouse to examine the effects of a high fat diet on this organ. Multivariate statistics readily separated tissue from PGC-1β null mice from their wild type controls either in gender specific models or in combined datasets. This was associated with an increase in creatine and a decrease in taurine in the null mouse, and an increase in myristic acid and a reduction in long chain polyunsaturated fatty acids for both genders. The most profound changes were detected by liquid chromatography mass spectrometry analysis of intact lipids with the tissue from the null mouse having a profound increase in a number of triglycerides. The metabolomic and lipodomic changes indicate PGC-1β has a profound influence on cardiac metabolism.
Keywords: metabolic syndrome; obesity; peroxisome proliferator activated receptors; peroxisome proliferator-activated receptor-γ coactivator 1-β; functional genomics metabolic syndrome; obesity; peroxisome proliferator activated receptors; peroxisome proliferator-activated receptor-γ coactivator 1-β; functional genomics
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

McCombie, G.; Medina-Gomez, G.; Lelliott, C.J.; Vidal-Puig, A.; Griffin, J.L. Metabolomic and Lipidomic Analysis of the Heart of Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-β Knock Out Mice on a High Fat Diet. Metabolites 2012, 2, 366-381.

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