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dc.contributor.authorRodriguez-Cuenca, Sergio
dc.contributor.authorCarobbio, Stefania
dc.contributor.authorBarceló-Coblijn, Gwendolyn
dc.contributor.authorPrieur, Xavier
dc.contributor.authorRelat, Joana
dc.contributor.authorAmat, Ramon
dc.contributor.authorCampbell, Mark
dc.contributor.authorDias, Ana Rita
dc.contributor.authorBahri, Myriam
dc.contributor.authorGray, Sarah L
dc.contributor.authorVidal-Puig, Antonio
dc.date.accessioned2018-09-08T06:33:48Z
dc.date.available2018-09-08T06:33:48Z
dc.date.issued2018-10
dc.identifier.issn1462-8902
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279892
dc.description.abstractFamilial partial lipodystrophic syndrome 3 (FPLD3) is associated with mutations in the transcription factor PPAR. One of these mutations, the P467L, confers a dominant negative effect. We and others have previously investigated the pathophysiology associated to this mutation using a humanised mouse model that recapitulated most of the clinical symptoms observed in human patients under different experimental conditions. One of the key clinical manifestations observed both in humans and mouse models is the ectopic accumulation of fat in the liver. Here, we dissect the molecular mechanisms that contribute to the excessive accumulation of lipids in the liver and characterise the negative effect of this PPAR mutation on the activity of PPAR in vivo when activated by fibrates. P465L mice have increased levels of insulin and free fatty acids (FFA), exhibit decreased levels of Very Low Density Lipoproteins (VLDL) when fed high fat diet (HFD) and partial impaired response to the hypolipidemic action of WY14643. This indicates that the deleterious effects of P465L-PPAR mutation may be augmented by their collateral negative effect on PPAR function.
dc.description.sponsorshipWellcome Trust, MRC MDU (MC_UU_12012/2), FP7-MITIN (Integration of the System Models of Mitochondrial Function and Insulin Signaling and its Application in the Study of Complex Diseases) (Grant Agreement 223450) and H2020 EPoS (Elucidating Pathways of Steatohepatitis) (Grant Agreement 634413). Disease Model Core, Biochemistry Assay Lab and the Histology Core are funded by MRC_MC_UU_12012/5 and a Wellcome Trust Strategic Award [100574/Z/12/Z]
dc.languageen
dc.publisherWiley
dc.titleP465L-PPARγ mutation confers partial resistance to the hypolipidaemic action of fibrates
dc.typeArticle
prism.endingPage2350
prism.issueIdentifier10
prism.publicationDate2018
prism.publicationNameDiabetes, Obesity and Metabolism
prism.startingPage2339
prism.volume20
dc.identifier.doi10.17863/CAM.27260
dcterms.dateAccepted2018-05-12
rioxxterms.versionofrecord10.1111/dom.13370
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-10
dc.contributor.orcidRodriguez-Cuenca, Sergio [0000-0001-9635-0504]
dc.contributor.orcidVidal-Puig, Antonio [0000-0003-4220-9577]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_12012/2)
pubs.funder-project-idEuropean Commission (223450)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (634413)
cam.issuedOnline2018-06-27
rioxxterms.freetoread.startdate2019-05-22


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