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

Higgins, Larry G.; Garbacz, Wojciech G.; Gustafsson, Mattias LU ; Nainamalai, Sitheswaran; Ashby, Peter R.; Wolf, C. Roland and Palmer, Colin N. A. (2012) In PPAR Research
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PPAR Research
publisher
Hindawi Publishing Corporation
external identifiers
  • wos:000302734200001
  • scopus:84859776080
ISSN
1687-4757
DOI
10.1155/2012/216817
language
English
LU publication?
yes
id
017b2746-f032-4160-a901-96c163a17526 (old id 2587332)
date added to LUP
2012-06-01 09:36:02
date last changed
2017-01-01 03:26:41
@article{017b2746-f032-4160-a901-96c163a17526,
  abstract     = {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.},
  articleno    = {216817},
  author       = {Higgins, Larry G. and Garbacz, Wojciech G. and Gustafsson, Mattias and Nainamalai, Sitheswaran and Ashby, Peter R. and Wolf, C. Roland and Palmer, Colin N. A.},
  issn         = {1687-4757},
  language     = {eng},
  publisher    = {Hindawi Publishing Corporation},
  series       = {PPAR Research},
  title        = {Conditional Expression of Human PPAR delta and a Dominant Negative Variant of hPPAR delta In Vivo},
  url          = {http://dx.doi.org/10.1155/2012/216817},
  year         = {2012},
}