Journal
SCIENCE
Volume 289, Issue 5484, Pages 1524-1529Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.289.5484.1524
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R37HL009610] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R37 HL 09610] Funding Source: Medline
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Several nuclear hormone receptors involved in lipid metabolism form obligate heterodimers with retinoid X receptors (RXRs) and are activated by RXR agonists such as rexinoids. Animals treated with rexinoids exhibited marked changes in cholesterol balance, including inhibition of cholesterol absorption and repressed bile acid synthesis. Studies with receptor-selective agonists revealed that oxysterol receptors (LXRs) and the bile acid receptor (FXR) are the RXR heterodimeric partners that mediate these effects by regulating expression of the reverse cholesterol transporter, ABC1, and the rate-limiting enzyme of bile acid synthesis, CYP7A1, respectively. Thus, these RXR heterodimers serve as key regulators of cholesterol homeostasis by governing reverse cholesterol transport from peripheral tissues, bile acid synthesis in Liver, and cholesterol absorption in intestine.
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