Identification of a nuclear receptor for bite acids

Makoto Makishima, Arthur Y. Okamoto, Joyce J. Repa, Hua Tu, R. Marc Learned, Alvin Luk, Mitchell V. Hull, Kevin D. Lustig, David J. Mangelsdorf, Bei Shan

Research output: Contribution to journalArticle

1808 Scopus citations

Abstract

Bite acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bite acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bite acids, FXR repressed transcription of the gene encoding cholesterol 7α- hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.

Original languageEnglish (US)
Pages (from-to)1362-1365
Number of pages4
JournalScience
Volume284
Issue number5418
DOIs
StatePublished - May 21 1999

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    Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., Hull, M. V., Lustig, K. D., Mangelsdorf, D. J., & Shan, B. (1999). Identification of a nuclear receptor for bite acids. Science, 284(5418), 1362-1365. https://doi.org/10.1126/science.284.5418.1362