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Conditional Expression of Human PPAR delta and a Dominant Negative Variant of hPPAR delta In Vivo

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Author

  • Larry G. Higgins
  • Wojciech G. Garbacz
  • Mattias Gustafsson
  • Sitheswaran Nainamalai
  • Peter R. Ashby
  • C. Roland Wolf
  • Colin N. A. Palmer

Summary, in English

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

Publishing year

2012

Language

English

Publication/Series

PPAR Research

Document type

Journal article

Publisher

Hindawi Limited

Topic

  • Microbiology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 1687-4757