Publication Date:
2000-09-01
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Repa, J J -- Turley, S D -- Lobaccaro, J A -- Medina, J -- Li, L -- Lustig, K -- Shan, B -- Heyman, R A -- Dietschy, J M -- Mangelsdorf, D J -- R37 HL 09610/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1524-9.〈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 75390-9050, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10968783" target="_blank"〉PubMed〈/a〉
Keywords:
ATP Binding Cassette Transporter 1
;
ATP-Binding Cassette Transporters/genetics/*metabolism
;
Animals
;
Bile Acids and Salts/biosynthesis
;
Biological Transport/drug effects
;
Cholesterol/*metabolism
;
Cholesterol 7-alpha-Hydroxylase/metabolism
;
Cholesterol, Dietary/administration & dosage
;
Cricetinae
;
DNA-Binding Proteins/metabolism
;
Dimerization
;
Gene Expression Regulation/drug effects
;
Glycoproteins/genetics/*metabolism
;
Homeostasis/drug effects
;
Intestinal Absorption/*drug effects
;
Intestine, Small/*metabolism
;
Ligands
;
Liver/*metabolism
;
Macrophages, Peritoneal/metabolism
;
Male
;
Mesocricetus
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Orphan Nuclear Receptors
;
*Receptors, Cytoplasmic and Nuclear
;
Receptors, Retinoic Acid/agonists/genetics/*metabolism
;
Receptors, Thyroid Hormone/agonists/genetics/metabolism
;
Retinoid X Receptors
;
Transcription Factors/agonists/*metabolism
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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