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PPAR Research
Volume 2012 (2012), Article ID 216817, 12 pages
http://dx.doi.org/10.1155/2012/216817
Research Article

Conditional Expression of Human PPARδ and a Dominant Negative Variant of hPPARδ In Vivo

1CRUK Molecular Pharmacology Unit, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
2Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Sölvegatan 23, SE-223 62 Lund, Sweden
3Division of Molecular Medicine, Medical Science Institute, College of Life Sciences, University of Dundee, Dundee DD1 4HN, UK

Received 21 September 2011; Revised 7 December 2011; Accepted 20 December 2011

Academic Editor: James P. Hardwick

Copyright © 2012 Larry G. Higgins et al. 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.

Abstract

The nuclear receptor, NR1C2 or peroxisome proliferator-activated receptor (PPAR)-δ, is ubiquitously expressed and important for placental development, fatty acid metabolism, wound healing, inflammation, and tumour development. PPARδ 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 PPARδ 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 PPARδ. Expression of either functional or dominant negative hPPARδ blocked bezafibrate-induced PPARα-dependent hepatomegaly and blocked the effect of bezafibrate on the transcription of PPARα target genes. These data demonstrate, for the first time, that PPARδ could inhibit the activation of PPARα in vivo and provide novel models for the investigation of the role of PPARδ in pathophysiology.