Linked Life Data

16002078

Source:http://linkedlifedata.com/resource/pubmed/id/16002078

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-25
pubmed:abstractText
A novel animal model of insulin resistance, the fructose-fed Syrian golden hamster, was employed to investigate the efficacy and mechanisms of action of rosuvastatin, a HMG-CoA reductase inhibitor, in ameliorating metabolic dyslipidemia in insulin-resistant states. Fructose feeding for a 2-week period induced insulin resistance and a significant increase in hepatic secretion of VLDL. This was followed by a fructose-enriched diet with or without 10 mg/kg rosuvastatin for 14 days. Fructose feeding in the first 2 weeks caused a significant increase in plasma total cholesterol and triglyceride in both groups (n=6, p<0.001). However, there was a significant decline (30%, n=8, p<0.05) in plasma triglyceride levels following rosuvastatin feeding (10 mg/kg). A significant decrease (n=6, p<0.05) was also observed in VLDL-apoB production in hepatocytes isolated from drug-treated hamsters, together with an increased apoB degradation (n=6, p<0.05). Similar results were obtained in parallel cell culture experiments in which primary hepatocytes were first isolated from chow-fed hamsters, and then treated in vitro with 15 microM rosuvastatin for 18 h. Rosuvastatin at 5 microM caused a substantial reduction in synthesis of unesterified cholesterol and cholesterol ester (98 and 25%, n=9, p<0.01 or p<0.05) and secretion of newly synthesized unesterified cholesterol, cholesterol ester, and triglyceride (95, 42, and 60% reduction, respectively, n=9, p<0.01 or p<0.05). This concentration of rosuvastatin also caused a significant reduction (75% decrease, n=4, p<0.01) in the extracellular secretion of VLDL-apoB100, accompanied by a significant increase in the intracellular degradation of apoB100. There was a 12% reduction (not significant, p>0.05) in hepatic MTP and no changes in ER-60 (a chaperone involved in apoB degradation) protein levels. Taken together, these data suggest that the assembly and secretion of VLDL particles in hamster hepatocytes can be acutely inhibited by rosuvastatin in a process involving enhanced apoB degradation. This appears to lead to a significant amelioration of hepatic VLDL-apoB overproduction observed in the fructose-fed, insulin-resistant hamster model.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9150
pubmed:author
pubmed:issnType
Print
pubmed:volume
185
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16002078-Animals, pubmed-meshheading:16002078-Apolipoproteins B, pubmed-meshheading:16002078-Cells, Cultured, pubmed-meshheading:16002078-Chromatography, Gel, pubmed-meshheading:16002078-Cricetinae, pubmed-meshheading:16002078-Disease Models, Animal, pubmed-meshheading:16002078-Dose-Response Relationship, Drug, pubmed-meshheading:16002078-Dyslipidemias, pubmed-meshheading:16002078-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16002078-Fluorobenzenes, pubmed-meshheading:16002078-Hepatocytes, pubmed-meshheading:16002078-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:16002078-Insulin Resistance, pubmed-meshheading:16002078-Liver, pubmed-meshheading:16002078-Male, pubmed-meshheading:16002078-Mesocricetus, pubmed-meshheading:16002078-Metabolic Syndrome X, pubmed-meshheading:16002078-Pyrimidines, pubmed-meshheading:16002078-Sulfonamides
pubmed:year
2006
pubmed:articleTitle
Effect of rosuvastatin on hepatic production of apolipoprotein B-containing lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia.
pubmed:affiliation
Division of Clinical Biochemistry, Research Institute, Hospital for Sick Children & Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ont., Canada M5G 1X8.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't