Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1998-7-6
pubmed:abstractText
We demonstrate that mice lacking the oxysterol receptor, LXR alpha, lose their ability to respond normally to dietary cholesterol and are unable to tolerate any amount of cholesterol in excess of that which they synthesize de novo. When fed diets containing cholesterol, LXR alpha (-/-) mice fail to induce transcription of the gene encoding cholesterol 7alpha-hydroxylase (Cyp7a), the rate-limiting enzyme in bile acid synthesis. This defect is associated with a rapid accumulation of large amounts of cholesterol in the liver that eventually leads to impaired hepatic function. The regulation of several other crucial lipid metabolizing genes is also altered in LXR alpha (-/-) mice. These results demonstrate the existence of a physiologically significant feed-forward regulatory pathway for sterol metabolism and establish the role of LXR alpha as the major sensor of dietary cholesterol.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Alkyl and Aryl Transferases, http://linkedlifedata.com/resource/pubmed/chemical/Bile Acids and Salts, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, Dietary, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol 7-alpha-Hydroxylase, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Farnesyl-Diphosphate..., http://linkedlifedata.com/resource/pubmed/chemical/Geranyltranstransferase, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl CoA Reductases, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides, http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0092-8674
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
693-704
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9630215-Alkyl and Aryl Transferases, pubmed-meshheading:9630215-Animals, pubmed-meshheading:9630215-Bile Acids and Salts, pubmed-meshheading:9630215-Cholesterol, pubmed-meshheading:9630215-Cholesterol, Dietary, pubmed-meshheading:9630215-Cholesterol 7-alpha-Hydroxylase, pubmed-meshheading:9630215-DNA-Binding Proteins, pubmed-meshheading:9630215-Down-Regulation, pubmed-meshheading:9630215-Farnesyl-Diphosphate Farnesyltransferase, pubmed-meshheading:9630215-Gene Expression Regulation, Enzymologic, pubmed-meshheading:9630215-Geranyltranstransferase, pubmed-meshheading:9630215-Hepatomegaly, pubmed-meshheading:9630215-Hydroxymethylglutaryl CoA Reductases, pubmed-meshheading:9630215-Hydroxymethylglutaryl-CoA Synthase, pubmed-meshheading:9630215-Liver, pubmed-meshheading:9630215-Mice, pubmed-meshheading:9630215-Mice, Knockout, pubmed-meshheading:9630215-Organ Size, pubmed-meshheading:9630215-Orphan Nuclear Receptors, pubmed-meshheading:9630215-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:9630215-Triglycerides
pubmed:year
1998
pubmed:articleTitle
Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha.
pubmed:affiliation
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 75235-9050, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't