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PMID: 9113986 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 9 ·1997-04-29 ·Pages 4312-7

Forman BM, Chen J, Evans RM

Abstract

Fatty acids (FAs) and their derivatives are essential cellular metabolites whose concentrations must be closely regulated. This implies that regulatory circuits exist which can sense changes in FA levels. Indeed, the peroxisome proliferator-activated receptor alpha (PPARalpha) regulates lipid homeostasis and is transcriptionally activated by a variety of lipid-like compounds. It remains unclear as to how these structurally diverse compounds can activate a single receptor. We have developed a novel conformation-based assay that screens activators for their ability to bind to PPARalpha/delta and induce DNA binding. We show here that specific FAs, eicosanoids, and hypolipidemic drugs are ligands for PPARalpha or PPARdelta. Because altered FA levels are associated with obesity, atherosclerosis, hypertension, and diabetes, PPARs may serve as molecular sensors that are central to the development and treatment of these metabolic disorders.

MeSH Terms
Eicosanoids/metabolism Fatty Acids, Unsaturated/metabolism Homeostasis Hypolipidemic Agents/metabolism Ligands Metabolic Diseases/etiology Receptors, Cytoplasmic and Nuclear/metabolism Transcription Factors/metabolism
Chemicals
Eicosanoids Fatty Acids, Unsaturated Hypolipidemic Agents Ligands Receptors, Cytoplasmic and Nuclear Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Forman B M
The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chen J
Evans R M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.9.4312
Published
1997-04-29
Pages
4312-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20719
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.94.9.4312 PMC Full Text View journal details
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