Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.
Détails
ID Serval
serval:BIB_1A59CC9FB332
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.
Périodique
Physiological Genomics
ISSN
1531-2267[electronic], 1094-8341[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
41
Numéro
1
Pages
42-52
Langue
anglais
Résumé
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.
Mots-clé
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
Création de la notice
08/03/2011 18:45
Dernière modification de la notice
20/08/2019 13:51