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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2005-8-1
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pubmed:abstractText |
The high-cholesterol/high-fat Western diet has abetted an epidemic of atherosclerotic cardiovascular disease, the leading cause of death in industrialized nations. Liver X receptors (LXRs) are oxysterol sensors that are required for normal cholesterol and triglyceride homeostasis, yet synthetic LXR agonists produce undesirable hypertriglyceridemia. Here we report a previously unrecognized role for hepatic LXRalpha in the links between diet, serum lipids, and atherosclerosis. A modest increase in hepatic LXRalpha worsened serum lipid profiles in LDL-receptor null mice fed normal chow but had the opposite effect on lipids and afforded strong protection against atherosclerosis on a Western diet. The beneficial effect of hepatic LXRalpha was abrogated by a synthetic LXR agonist, which activated SREBP-1c and its target genes. Thus, the interplay between diet and hepatic LXRalpha is a critical determinant of serum lipid profiles and cardiovascular risk, and selective modulation of LXR target genes in liver can ameliorate hyperlipidemia and cardiovascular disease.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anticholesteremic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrocarbons, Fluorinated,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/TO-901317,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1550-4131
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
1
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
297-308
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16054077-Animals,
pubmed-meshheading:16054077-Anticholesteremic Agents,
pubmed-meshheading:16054077-Arteriosclerosis,
pubmed-meshheading:16054077-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:16054077-Cardiovascular Diseases,
pubmed-meshheading:16054077-DNA-Binding Proteins,
pubmed-meshheading:16054077-Diet,
pubmed-meshheading:16054077-Female,
pubmed-meshheading:16054077-Gene Expression Regulation,
pubmed-meshheading:16054077-Humans,
pubmed-meshheading:16054077-Hydrocarbons, Fluorinated,
pubmed-meshheading:16054077-Lipid Metabolism,
pubmed-meshheading:16054077-Lipids,
pubmed-meshheading:16054077-Liver,
pubmed-meshheading:16054077-Male,
pubmed-meshheading:16054077-Mice,
pubmed-meshheading:16054077-Mice, Inbred C57BL,
pubmed-meshheading:16054077-Mice, Knockout,
pubmed-meshheading:16054077-Mice, Transgenic,
pubmed-meshheading:16054077-Orphan Nuclear Receptors,
pubmed-meshheading:16054077-RNA, Messenger,
pubmed-meshheading:16054077-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:16054077-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:16054077-Sulfonamides,
pubmed-meshheading:16054077-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha.
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pubmed:affiliation |
Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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