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The contrasting roles of PPARδ and PPARγ in regulating the metabolic switch between oxidation and storage of fats in white adipose tissue

Lee D Roberts12, Andrew J Murray3, David Menassa3, Tom Ashmore1, Andrew W Nicholls4 and Julian L Griffin1256*

Author Affiliations

1 Department of Biochemistry University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK

2 The Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK

3 Department of Physiology, Development and Neuroscience University of Cambridge, Downing Street, Cambridge CB2 3EG, UK

4 GlaxoSmithKline, Investigative Preclinical Toxicology, Park Road, Ware, SG12 0DP, UK

5 MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL, UK

6 The MRC Centre for Obesity and Related Disorders (CORD), Institute of Metabolic Sciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK

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Genome Biology 2011, 12:R75  doi:10.1186/gb-2011-12-8-r75

Published: 11 August 2011

Additional files

Additional file 1:

Figure S1 - M+1/M isotope ratio 13C enrichment of lactate, succinate, glutamate and arachidate. (a-c) M+1/M isotope ratio 13C enrichment of (a) lactate, (b) succinate and (c) glutamate analyzed by GC-MS of the aqueous fraction from control and PPARγ agonist-treated 3T3-L1 cells incubated with 1-13C-glucose. (d) M+1/M isotope ratio 13C enrichment of arachidate analyzed by GC-MS of the organic fraction from control and PPARγ agonist-treated 3T3-L1 cells incubated with 1-13C-glucose. *P < 0.05. The metabolites have been mapped to the glycolysis, TCA cycle and fatty acid synthesis metabolic pathways. An upward pointing arrows indicates a metabolite increased in 13C enrichment by PPARγ activation, and a downward pointing arrows indicates a metabolite decreased in 13C enrichment by PPARγ activation. Parent ions were used to calculate ion ratio.

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Open Data

Additional file 2:

Figure S2 - the average integrated area of the two-dimensional HSQC-NMR organic fraction glycerol peak. (a) A graph of the average integrated area of the two-dimensional HSQC-NMR organic fraction glycerol peak (13C chemical shift 62.04) from control and 1 μM PPARδ agonist-treated 3T3-L1 adipocytes incubated in 1-13C glucose. (b) A graph of the average integrated area of the two-dimensional HSQC-NMR organic fraction glycerol peak (13C chemical shift 62.17) from control and 1 μM PPARδ agonist-treated 3T3-L1 adipocytes incubated in 1-13C glucose. (c) A graph of the average integrated area of the two-dimensional HSQC-NMR organic fraction esterified glycerol peak from control and 1 μM PPARδ agonist-treated 3T3-L1 adipocytes incubated in 1-13C glucose. *P < 0.05, ***P < 0.005. Parent ions were used to calculate ion ratio.

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Open Data

Additional file 3:

Figure S3 - M+1/M isotope ratios. (a, b) The M+1/M isotope ratio 13C enrichment of (a) glutamate and (b) isocitrate analyzed by GC-MS of the aqueous fraction from control and PPARγ agonist-treated 3T3-L1 cells incubated with 13C-U-palmitate. (c-e) Graphs showing the isotope ratio 13C enrichment of myristate (c), arachidate (d) and palmitate (e) analyzed by GC-MS of the organic fraction from control and PPARγ agonist-treated 3T3-L1 cells incubated with 13C-U-palmitate. The metabolites have been mapped to the TCA cycle and fatty acid β-oxidation/synthesis metabolic pathways. Red indicates a metabolite increased in 13C enrichment by PPARγ activation. Blue indicates a metabolite decreased in 13C enrichment by PPARγ activation. *P < 0.05, **P < 0.01,***P < 0.005. Parent ions were used to calculate ion ratio.

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Open Data

Additional file 4:

Figure S4 - the effect of PPARγ activation on the integration of the energy metabolism pathways of 3T3-L1 adipocytes. A diagram showing the effect of PPARγ activation on the integration of the energy metabolism pathways of 3T3-L1 adipocytes based on the combination of results from the metabolomic, transcriptomic and stable isotope labeling studies. Red indicates an increase in concentration or expression in cells treated with the PPARγ selective agonist GW347845. Blue indicates a decrease in concentration in cells treated with the PPARγ selective agonist GW347845.

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Open Data