Publication Date:
1999-05-21
Description:
Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- New York, N.Y. -- Science. 1999 May 21;284(5418):1362-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10334992" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bile Acids and Salts/biosynthesis/*metabolism
;
Biological Transport
;
Carrier Proteins/*genetics/metabolism
;
Cell Line
;
Chenodeoxycholic Acid/*metabolism
;
Cholesterol/metabolism
;
Cholesterol 7-alpha-Hydroxylase/*genetics
;
DNA-Binding Proteins/chemistry/genetics/*metabolism
;
Gene Expression Regulation
;
Histone Acetyltransferases
;
Homeostasis
;
Humans
;
*Hydroxysteroid Dehydrogenases
;
Ligands
;
Liver/metabolism
;
*Membrane Glycoproteins
;
Mice
;
Nuclear Receptor Coactivator 1
;
*Organic Anion Transporters, Sodium-Dependent
;
Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism
;
*Symporters
;
Transcription Factors/chemistry/genetics/*metabolism
;
Transfection
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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