Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ

Proceedings of the National Academy of Sciences of the United States of America - Tập 94 Số 9 - Trang 4312-4317 - 1997
Barry M. Forman1, Jasmine Chen1, Ronald M. Evans1
1The Salk Institute for Biological Studies and Howard Hughes Medical Institute, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037

Tóm tắt

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 α (PPARα) 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 PPARα/δ and induce DNA binding. We show here that specific FAs, eicosanoids, and hypolipidemic drugs are ligands for PPARα or PPARδ. 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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 94 Số 9

4312-4317

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