Back to Search
Start Over
Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2003 May 02; Vol. 278 (18), pp. 15565-70. Date of Electronic Publication: 2003 Feb 22. - Publication Year :
- 2003
-
Abstract
- Liver X receptor (LXR) is a nuclear receptor that plays a crucial role in orchestrating the trafficking of sterols between tissues. Treatment of mice with a potent and specific LXR agonist, T0901317, is associated with increased biliary cholesterol secretion, decreased fractional cholesterol absorption, and increased fecal neutral sterol excretion. Here we show that expression of two target genes of LXRalpha, the ATP-binding cassette (ABC) transporters Abcg5 and Abcg8, is required for both the increase in sterol excretion and the decrease in fractional cholesterol absorption associated with LXR agonist treatment. Mice expressing no ABCG5 and ABCG8 (G5G8(-/-) mice) and their littermate controls were treated for 7 days with T0901317. In wild type animals, treatment with the LXR agonist resulted in a 3-fold increase in biliary cholesterol concentrations, a 25% reduction in fractional cholesterol absorption, and a 4-fold elevation in fecal neutral sterol excretion. In contrast, the LXR agonist did not significantly affect biliary cholesterol levels, fractional cholesterol absorption, or neutral fecal sterol excretion in the G5G8(-/-) mice. Thus Abcg5 and Abcg8 are required for LXR agonist-associated changes in dietary and biliary sterol trafficking. These results establish a central role for ABCG5 and ABCG8 in promoting cholesterol excretion in vivo.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily G, Member 5
ATP Binding Cassette Transporter, Subfamily G, Member 8
Animals
Bile metabolism
DNA-Binding Proteins
Feces chemistry
Hydrocarbons, Fluorinated
Liver metabolism
Liver X Receptors
Mice
Mice, Inbred C57BL
Orphan Nuclear Receptors
RNA, Messenger analysis
Receptors, Cytoplasmic and Nuclear agonists
Sitosterols metabolism
Sulfonamides
ATP-Binding Cassette Transporters physiology
Anticholesteremic Agents pharmacology
Cholesterol metabolism
Lipoproteins physiology
Receptors, Cytoplasmic and Nuclear physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 278
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12601003
- Full Text :
- https://doi.org/10.1074/jbc.M301311200