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


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

SUBMITTER: Higgins LG 

PROVIDER: S-EPMC3324915 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Higgins Larry G LG   Garbacz Wojciech G WG   Gustafsson Mattias C U MC   Nainamalai Sitheswaran S   Ashby Peter R PR   Wolf C Roland CR   Palmer Colin N A CN  

PPAR research 20120321


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  ...[more]

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