Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-7-20
pubmed:abstractText
The ATP binding cassette transporters ABCG5 (G5) and ABCG8 (G8) limit the accumulation of neutral sterols by restricting sterol uptake from the intestine and promoting sterol excretion into bile. Humans and mice lacking G5 and G8 (G5G8-/-) accumulate plant sterols in the blood and tissues. However, despite impaired biliary cholesterol secretion, plasma and liver cholesterol levels are lower in G5G8-/- mice than in wild-type littermates. To determine whether the observed changes in hepatic sterol metabolism were a direct result of decreased biliary sterol secretion or a metabolic consequence of the accumulation of dietary noncholesterol sterols, we treated G5G8-/- mice with ezetimibe, a drug that reduces the absorption of both plant- and animal-derived sterols. Ezetimibe feeding for 1 month sharply decreased sterol absorption and plasma levels of sitosterol and campesterol but increased cholesterol in both the plasma (from 60.4 to 75.2 mg/dl) and the liver (from 1.1 to 1.87 mg/g) of the ezetimibe-treated G5G8-/- mice. Paradoxically, the increase in hepatic cholesterol was associated with an increase in mRNA levels of HMG-CoA reductase and synthase. Together, these results indicate that pharmacological blockade of sterol absorption can ameliorate the deleterious metabolic effects of plant sterols even in the absence of G5 and G8.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ABCG5 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/ABCG8 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters, http://linkedlifedata.com/resource/pubmed/chemical/Azetidines, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Phytosterols, http://linkedlifedata.com/resource/pubmed/chemical/Sitosterols, http://linkedlifedata.com/resource/pubmed/chemical/Sterols, http://linkedlifedata.com/resource/pubmed/chemical/campesterol, http://linkedlifedata.com/resource/pubmed/chemical/ezetimibe, http://linkedlifedata.com/resource/pubmed/chemical/sitosterol
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1739-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Ezetimibe normalizes metabolic defects in mice lacking ABCG5 and ABCG8.
pubmed:affiliation
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural