Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.

Details

Serval ID
serval:BIB_1222
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Kliewer S.A., Sundseth S.S., Jones S.A., Brown P.J., Wisely G.B., Koble C.S., Devchand P., Wahli W., Willson T.M., Lenhard J.M., Lehmann J.M.
ISSN
0027-8424[print], 0027-8424[linking]
Publication state
Published
Issued date
1997
Volume
94
Number
9
Pages
4318-4323
Language
english
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2007 12:03
Last modification date
20/08/2019 12:40
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