Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.

Details

Serval ID
serval:BIB_1A59CC9FB332
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.
Journal
Physiological Genomics
Author(s)
Sanderson L.M., Boekschoten M.V., Desvergne B., Müller M., Kersten S.
ISSN
1531-2267[electronic], 1094-8341[linking]
Publication state
Published
Issued date
2010
Volume
41
Number
1
Pages
42-52
Language
english
Abstract
Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) beta/delta in liver. Here we set out to better elucidate the function of PPARbeta/delta in liver by comparing the effect of PPARalpha and PPARbeta/delta deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARalpha and PPARbeta/delta deletion was similar, whereas in fasted state the effect of PPARalpha deletion was much more pronounced, consistent with the pattern of gene expression of PPARalpha and PPARbeta/delta. Minor overlap was found between PPARalpha- and PPARbeta/delta-dependent gene regulation in liver. Pathways upregulated by PPARbeta/delta deletion were connected to innate immunity and inflammation. Pathways downregulated by PPARbeta/delta deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARbeta/delta-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARbeta/delta target genes. In contrast to PPARalpha-/- mice, no changes in plasma free fatty acid, plasma beta-hydroxybutyrate, liver triglycerides, and liver glycogen were observed in PPARbeta/delta-/- mice. Our data indicate that PPARbeta/delta governs glucose utilization and lipoprotein metabolism and has an important anti-inflammatory role in liver. Overall, our analysis reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.
Keywords
Animals, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Immunity/genetics, Inflammation/genetics, Liver/metabolism, Metabolome/genetics, Mice, Oligonucleotide Array Sequence Analysis, PPAR alpha/deficiency, PPAR alpha/genetics, PPAR delta/deficiency, PPAR delta/genetics, PPAR-beta/deficiency, PPAR-beta/genetics, Transcription, Genetic
Pubmed
Web of science
Create date
08/03/2011 17:45
Last modification date
20/08/2019 12:51
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