Andy, Here's some detail on PPARs and metabolic diseases:
Proc Natl Acad Sci U S A 1997 Apr 29;94(9):4312-4317
Hypolipidemic drugs, polyunsaturated fatty acids, and
eicosanoids are ligands for peroxisome
proliferator-activated receptors alpha and delta.
Forman BM, Chen J, Evans RM
The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines
Road, La Jolla, CA 92037, USA.
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.
PMID: 9113986, UI: 97272220 |
