Transcriptomics

Dataset Information

0

Molecular characterization of novel peroxisome proliferator-activated receptor alpha agonists


ABSTRACT: The nuclear receptor PPARalpha is recognized as the primary target of the fibrate class of hypolipidemic drugs and mediates lipid lowering in part by activating a transcriptional cascade that induces genes involved in the catabolism of lipids. We report here the characterization of three novel PPARalpha agonists with therapeutic potential for treating dyslipidemia. These structurally related compounds display potent and selective binding to human PPARalpha and support robust recruitment of coactivator peptides in vitro. These compounds markedly potentiate chimeric transcription systems in cell-based assays and strikingly lower serum triglycerides in vivo. The transcription networks induced by these selective PPARalpha agonists were assessed by transcriptional profiling of mouse liver after acute and chronic treatment. The induction of several known PPARalpha target genes involved with fatty acid metabolism were observed, reflecting the expected pharmacology associated with PPARalpha activation. We also noted the downregulation of a number of genes related to immune cell function, the acute phase response, and glucose metabolism; suggesting that these compounds may have anti-inflammatory action in the mammalian liver. Taken together, these studies articulate the therapeutic promise of a selective PPARalpha agonist. Keywords: acute versus chronic treatment of piperidine PPARalpha agonists

ORGANISM(S): Mus musculus

PROVIDER: GSE12147 | GEO | 2008/11/25

SECONDARY ACCESSION(S): PRJNA113757

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2008-12-02 | E-GEOD-12147 | biostudies-arrayexpress
2006-06-20 | GSE5100 | GEO
2011-10-18 | GSE33044 | GEO
2013-03-13 | GSE43278 | GEO
2011-10-17 | E-GEOD-33044 | biostudies-arrayexpress
2022-10-31 | GSE159086 | GEO
2012-04-18 | E-GEOD-32121 | biostudies-arrayexpress
| PRJNA95355 | ENA
2014-12-08 | GSE45923 | GEO
2014-12-08 | E-GEOD-45923 | biostudies-arrayexpress