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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Andrew H who wrote (15135)	2/15/1998 4:10:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Andy, I was referring to energy metabolism. AIDS patients on PIs not only have their fat rearranged, but they also run into problems with diabetes. Energy metabolism and insulin resistance are controlled by the same general classes of receptors. The critical heteropulex for insulin resistance is PPAR gamma paired up with RXR alpha (which is activated by Targretin). For energy metabolism, its PPAR alpha, also paired up with an RXR (it may also be alpha, but the subtype is irrelevant because Targretin activates all three RXR subtypes).

To: Andrew H who wrote (15135)	2/19/1998 12:33:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

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