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PPAR<jats:italic>\u03b4<\/jats:italic>has been hypothesized to function as both a ligand activated transcription factor and a repressor of transcription in the absence of agonist. In this paper, treatment of mice conditionally expressing human PPAR<jats:italic>\u03b4<\/jats:italic>with GW501516 resulted in a marked loss in body weight that was not evident in nontransgenic animals or animals expressing a dominant negative derivative of PPAR<jats:italic>\u03b4<\/jats:italic>. Expression of either functional or dominant negative hPPAR<jats:italic>\u03b4<\/jats:italic>blocked bezafibrate-induced PPAR<jats:italic>\u03b1<\/jats:italic>-dependent hepatomegaly and blocked the effect of bezafibrate on the transcription of PPAR<jats:italic>\u03b1<\/jats:italic>target genes. These data demonstrate, for the first time, that PPAR<jats:italic>\u03b4<\/jats:italic>could inhibit the activation of PPAR<jats:italic>\u03b1 in vivo<\/jats:italic>and provide novel models for the investigation of the role of PPAR<jats:italic>\u03b4<\/jats:italic>in pathophysiology.<\/jats:p>","DOI":"10.1155\/2012\/216817","type":"journal-article","created":{"date-parts":[[2012,3,23]],"date-time":"2012-03-23T01:05:10Z","timestamp":1332464710000},"page":"1-12","source":"Crossref","is-referenced-by-count":6,"title":["Conditional Expression of Human PPAR<i>\u03b4<\/i>and a Dominant Negative Variant of hPPAR<i>\u03b4 In Vivo<\/i>"],"prefix":"10.1155","volume":"2012","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9755-2260","authenticated-orcid":true,"given":"Larry G.","family":"Higgins","sequence":"first","affiliation":[{"name":"CRUK Molecular Pharmacology Unit, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech G.","family":"Garbacz","sequence":"additional","affiliation":[{"name":"CRUK Molecular Pharmacology Unit, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3260-0724","authenticated-orcid":true,"given":"Mattias C. 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