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rdf:type |
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lifeskim:mentions |
umls-concept:C0015688,
umls-concept:C0023977,
umls-concept:C0034693,
umls-concept:C0036536,
umls-concept:C0036537,
umls-concept:C0086045,
umls-concept:C0205054,
umls-concept:C0286651,
umls-concept:C0301630,
umls-concept:C0441994,
umls-concept:C1157337
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pubmed:issue |
2-3
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pubmed:dateCreated |
2002-3-6
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pubmed:abstractText |
The mechanism by which atorvastatin lowers plasma triglyceride (TG) levels is mainly through a decrease in hepatic TG secretion. However, it is not clear why atorvastatin, which does not inhibit TG synthesis in vitro, decreases hepatic TG secretion without a prospective increase in hepatic TG concentration. For the investigation of the mechanisms that underlie the hypotriglyceridemic effects of atorvastatin, we characterized the effect of either a single or an 11 day administration of atorvastatin in sucrose-induced hypertriglyceridemic rats. Atorvastatin (30 mg/kg p.o.) strongly decreased the rate of both very-low-density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B secretion. The inhibitor also decreased hepatic TG concentration. Hepatic TG synthesis activity was also decreased by atorvastatin, and its activity was correlated with both hepatic and plasma TG concentration. There was also a strong correlation between the hepatic TG synthesis and hepatic non-esterified fatty acid (NEFA) concentration (r(2)=0.815). These effects required chronic administration of the inhibitor and were not observed by acute treatment. Repeated administration of atorvastatin also strongly reduced hepatic acyl-coenzyme A synthase mRNA levels. These results suggest that the reduced hepatic NEFA most likely lowers hepatic TG synthesis and TG secretion in sucrose-fed hypertriglyceridemic rats.
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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/Apolipoproteins B,
http://linkedlifedata.com/resource/pubmed/chemical/Coenzyme A Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Sucrose,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Nonesterified,
http://linkedlifedata.com/resource/pubmed/chemical/Heptanoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Lipase,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, VLDL,
http://linkedlifedata.com/resource/pubmed/chemical/Oleic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/atorvastatin,
http://linkedlifedata.com/resource/pubmed/chemical/very low density lipoprotein...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-3002
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
1580
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
161-70
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11880241-Animals,
pubmed-meshheading:11880241-Anticholesteremic Agents,
pubmed-meshheading:11880241-Apolipoproteins B,
pubmed-meshheading:11880241-Coenzyme A Ligases,
pubmed-meshheading:11880241-Dietary Sucrose,
pubmed-meshheading:11880241-Disease Models, Animal,
pubmed-meshheading:11880241-Down-Regulation,
pubmed-meshheading:11880241-Fatty Acids, Nonesterified,
pubmed-meshheading:11880241-Heptanoic Acids,
pubmed-meshheading:11880241-Hypertriglyceridemia,
pubmed-meshheading:11880241-Lipase,
pubmed-meshheading:11880241-Lipoproteins, VLDL,
pubmed-meshheading:11880241-Liver,
pubmed-meshheading:11880241-Male,
pubmed-meshheading:11880241-Oleic Acid,
pubmed-meshheading:11880241-Pyrroles,
pubmed-meshheading:11880241-RNA, Messenger,
pubmed-meshheading:11880241-Rats,
pubmed-meshheading:11880241-Rats, Sprague-Dawley,
pubmed-meshheading:11880241-Triglycerides,
pubmed-meshheading:11880241-Tritium
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pubmed:year |
2002
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pubmed:articleTitle |
Reduction in hepatic non-esterified fatty acid concentration after long-term treatment with atorvastatin lowers hepatic triglyceride synthesis and its secretion in sucrose-fed rats.
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pubmed:affiliation |
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Co., Ltd., Ibaraki, Japan. funatsu@yamanouchi.co.jp
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pubmed:publicationType |
Journal Article
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