Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.

Détails

ID Serval
serval:BIB_93B0C2E8F4DA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.
Périodique
Molecular and Cellular Biology
Auteur(s)
Sanderson L.M., Degenhardt T., Koppen A., Kalkhoven E., Desvergne B., Müller M., Kersten S.
ISSN
1098-5549[electronic], 0270-7306[linking]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
29
Numéro
23
Pages
6257-6267
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARalpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARbeta/delta. In contrast, the data did not support activation of PPARalpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs.
Mots-clé
Adipose Tissue/metabolism, Animals, Cell Line, Tumor, Fasting, Fatty Acids/blood, Gene Expression Regulation/drug effects, Humans, Liver/metabolism, Mice, Mice, Knockout, PPAR alpha/agonists, PPAR alpha/deficiency, PPAR-beta/metabolism, Peroxisome Proliferators/pharmacology, Pyrimidines/pharmacology, Rats, Receptors, Cytoplasmic and Nuclear/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/11/2009 13:07
Dernière modification de la notice
08/05/2019 22:11
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