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A potential therapeutic mechanism for regulating cholesterol uptake

Retinoid receptors play a key part in cholesterol homeostasis.

By | September 5, 2000

LONDON, September 5 (SPIS MedWire). Cholesterol homeostasis is regulated in large part by retinoid X receptors (RXR), according to animal research reported in the journal Science. A multicenter US team, led by J. Repa from Howard Hughes Medical Institute, studied mice fed rexinoid LG268, an RXR agonist. This resulted in marked changes in cholesterol balance, including inhibition of cholesterol absorption and repressed bile acid synthesis. Studies with receptor-selective agonists revealed that oxysterol receptors and the bile acid receptor are the RXR heterodimeric partners that mediate changes in cholesterol balance by regulating expression of the reverse cholesterol transporter, ABC1, and the rate-limiting enzyme of bile acid synthesis, CYP7A1, respectively. "The surprising discovery was that the drug inhibited the absorption of cholesterol and also induced expression in the peripheral tissues of a protein that causes the removal of cholesterol from the body," say the authors. The team believe that their research has identified proteins that are potentially "very important targets for drug therapy." They note several biotechnology companies are already modifying the drug used in the present study, rexinoid LG268, in order to overcome some of its unwanted side-effects.

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