| 摘要 |
Fatty acids (FAs) and their derivatives are essential cellular metabolites whose concentations must be closely regulated. This implies that regulatory circuits exist which can sense changes in FA levels. Indeed, the peroxisome proliferator activated receptor alpha (PPAR alpha ) 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. In accordance with the present invention, there are provided conformation-based assays which screen activators for their ability to bind to PPARs (i.e., PPAR alpha , PPAR delta and PPAR gamma ) and induce DNA binding. It is shown here that specific FAs, eicosanoids and lipomodulatory agents are ligands for PPAR alpha , PPAR delta and/or PPAR gamma . Since altered FA levels are associated with obesity, atherosclerosis, hypertension and diabetes, PPARs may serve as molecular sensors which are central to the development and treatment of these metabolic disorders.
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