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dc.contributor.authorRoberts, Lee Den
dc.contributor.authorMurray, Andrewen
dc.contributor.authorMenassa, Daviden
dc.contributor.authorAshmore, Tomen
dc.contributor.authorNicholls, Andrew Wen
dc.contributor.authorGriffin, Julianen
dc.date.accessioned2011-10-12T19:07:12Z
dc.date.available2011-10-12T19:07:12Z
dc.date.issued2011-08-11en
dc.identifier.issn1474-760X
dc.identifier.urihttp://www.dspace.cam.ac.uk/handle/1810/239219
dc.description.abstractAbstract Background The nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and peroxisome proliferator-activated receptor δ (PPARδ) play central roles in regulating metabolism in adipose tissue, as well as being targets for the treatment of insulin resistance. While the role of PPARγ in regulating insulin sensitivity has been well defined, research into PPARδ has been limited until recently due to a scarcity of selective PPARδ agonists. Results The metabolic effects of PPARγ and PPARδ activation have been examined in vivo in white adipose tissue from ob/ob mice and in vitro in cultured 3T3-L1 adipocytes using 1H nuclear magnetic resonance spectroscopy and mass spectrometry metabolomics to understand the receptors' contrasting roles. These steady state measurements were supplemented with 13C-stable isotope substrate labeling to assess fluxes, in addition to respirometry and transcriptomic microarray analysis. The metabolic effects of the receptors were readily distinguished, with PPARγ activation characterized by increased fat storage, synthesis and elongation, while PPARδ activation caused increased fatty acid β-oxidation, tricarboxylic acid cycle rate and oxidation of extracellular branch chain amino acids. Stimulated glycolysis and increased fatty acid desaturation were common pathways for the agonists. Conclusions PPARγ and PPARδ restore insulin sensitivity through varying mechanisms. PPARδ activation increases total oxidative metabolism in white adipose tissue, a tissue not traditionally thought of as oxidative. However, the increased metabolism of branch chain amino acids may provide a mechanism for muscle atrophy, which has been linked to activation of this nuclear receptor. PPARδ has a role as an anti-obesity target and as an anti-diabetic, and hence may target both the cause and consequences of dyslipidemia.
dc.titleThe contrasting roles of PPARdelta and PPARgamma in regulating the metabolic switch between oxidation and storage of fats in white adipose tissueen
dc.typeArticle
dc.date.updated2011-10-12T19:07:12Z
dc.description.versionRIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.en
dc.language.rfc3066en
dc.rights.holderRoberts et al.; licensee BioMed Central Ltd.
prism.publicationDate2011en
dcterms.dateAccepted2011-08-11en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2011-08-11en
dc.contributor.orcidMurray, Andrew [0000-0002-0929-9315]
dc.contributor.orcidGriffin, Julian [0000-0003-1336-7744]
dc.identifier.eissn1474-760X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/D524824/1)
pubs.funder-project-idBBSRC (BB/H013539/1)
pubs.funder-project-idWellcome Trust (078652/Z/05/Z)


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