Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers

J. J. Repa, S. D. Turley, J. M A Lobaccaro, J. Medina, L. Li, K. Lustig, B. Shan, R. A. Heyman, J. M. Dietschy, D. J. Mangelsdorf

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Abstract

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 bite acid synthesis. Studies with receptor-selective agonists revealed that oxysterol receptors (LXRs) and the bite 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 bite 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.

Original languageEnglish (US)
Pages (from-to)1524-1529
Number of pages6
JournalScience
Volume289
Issue number5484
DOIs
StatePublished - Sep 1 2000

ASJC Scopus subject areas

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    Repa, J. J., Turley, S. D., Lobaccaro, J. M. A., Medina, J., Li, L., Lustig, K., Shan, B., Heyman, R. A., Dietschy, J. M., & Mangelsdorf, D. J. (2000). Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science, 289(5484), 1524-1529. https://doi.org/10.1126/science.289.5484.1524