BES2003 Symposia Hot Topics (3 abstracts)
A natural product that lowers cholesterol as an antagonist for the bile acid receptor FXR
NL Urizar 1 , A Liverman 2 , P Ordentlich 3 , Y Yan 3 , RA Heyman 3 , FJ Gonzalez 4 , DJ Mangelsdorf 2 & DD Moore 1
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; 2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3X-Ceptor Therapeutics, Inc., San Diego, CA, USA; 4National Cancer Institute, National Insitutes of Health, Bethesda, MD, USA.
The resin of the guggul tree (Commiphora mukul) has been used for millennia in Ayurvedic medicine to treat a variety of ailments. Extracts of this resin have been reported to lower LDL cholesterol in humans, and the plant sterol guggulsterone (4,17(20)-pregnadiene-3,16-dione) is thought to be the active agent. We have found that guggulsterone is an antagonist ligand for the nuclear the bile acid receptor, FXR. Guggulsterone treatment lowers hepatic cholesterol levels in wild type mice fed a high cholesterol diet, but this effect is absent in FXR null mice. Thus, we suggest that inhibition of FXR activation is the basis for the lipid lowering activity of guggulsterone.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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