Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.
Détails
ID Serval
serval:BIB_1222
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424[print], 0027-8424[linking]
Statut éditorial
Publié
Date de publication
1997
Volume
94
Numéro
9
Pages
4318-4323
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are key regulators of lipid homeostasis and are activated by a structurally diverse group of compounds including fatty acids, eicosanoids, and hypolipidemic drugs such as fibrates and thiazolidinediones. While thiazolidinediones and 15-deoxy-Delta12, 14-prostaglandin J2 have been shown to bind to PPARgamma, it has remained unclear whether other activators mediate their effects through direct interactions with the PPARs or via indirect mechanisms. Here, we describe a novel fibrate, designated GW2331, that is a high-affinity ligand for both PPARalpha and PPARgamma. Using GW2331 as a radioligand in competition binding assays, we show that certain mono- and polyunsaturated fatty acids bind directly to PPARalpha and PPARgamma at physiological concentrations, and that the eicosanoids 8(S)-hydroxyeicosatetraenoic acid and 15-deoxy-Delta12,14-prostaglandin J2 can function as subtype-selective ligands for PPARalpha and PPARgamma, respectively. These data provide evidence that PPARs serve as physiological sensors of lipid levels and suggest a molecular mechanism whereby dietary fatty acids can modulate lipid homeostasis.
Mots-clé
Animals, Antilipemic Agents/metabolism, Binding, Competitive, Butyrates/metabolism, Eicosanoids/metabolism, Fatty Acids/metabolism, Gene Expression Regulation, Humans, Ligands, Mice, Phenylurea Compounds/metabolism, Receptors, Cytoplasmic and Nuclear/classification, Receptors, Cytoplasmic and Nuclear/genetics, Recombinant Fusion Proteins/metabolism, Species Specificity, Transcription Factors/classification, Transcription Factors/genetics, Xenopus
OAI-PMH
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 13:03
Dernière modification de la notice
20/08/2019 13:40