Linked Life Data

19362162

Source:http://linkedlifedata.com/resource/pubmed/id/19362162

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-7-20
pubmed:abstractText
Mice have been used widely to define the mechanism of action of fibric acid derivatives. The fibrates are pharmacological agonists of the peroxisome proliferator-activated receptor alpha (PPARalpha), whose activation in human subjects promotes potent reduction in plasma levels of triglycerides (TG) with concomitant increase in those of HDL-cholesterol. The impact of PPARalpha agonists on gene expression in humans and rodents is however distinct; such distinctions include differential regulation of key genes of lipid metabolism. We evaluated the question as to whether the human and murine genes encoding apolipoprotein apoAV, a regulator of plasma concentrations of TG-rich lipoproteins, might be differentially regulated in response to fibrates. Fenofibrate, a classic PPARalpha agonist, repressed expression of mouse Apoa5 in vivo in a mouse model transgenic for the human APOA5 gene; by contrast, expression of the human ortholog was up-regulated. Our findings are consistent with the presence of a functional PPAR-binding element in the promoter of the human APOA5 gene; this element is however degenerate and non-functional in the corresponding mouse Apoa5 sequence, as demonstrated by reporter assays and gel shift analyses. These data further highlights the distinct mechanisms which are implicated in the metabolism of TG-rich lipoproteins in mice as compared to man. They equally emphasize the importance of the choice of a mouse model for investigation of the impact of pharmaceutical modifiers on hypertriglyceridemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1791
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
764-71
pubmed:meshHeading
pubmed-meshheading:19362162-Animals, pubmed-meshheading:19362162-Apolipoproteins, pubmed-meshheading:19362162-Apolipoproteins A, pubmed-meshheading:19362162-Base Sequence, pubmed-meshheading:19362162-Cell Line, Tumor, pubmed-meshheading:19362162-Clofibric Acid, pubmed-meshheading:19362162-Down-Regulation, pubmed-meshheading:19362162-Gene Expression Regulation, pubmed-meshheading:19362162-Humans, pubmed-meshheading:19362162-Hypertriglyceridemia, pubmed-meshheading:19362162-Lipoproteins, pubmed-meshheading:19362162-Liver, pubmed-meshheading:19362162-Male, pubmed-meshheading:19362162-Mice, pubmed-meshheading:19362162-Mice, Transgenic, pubmed-meshheading:19362162-Molecular Sequence Data, pubmed-meshheading:19362162-PPAR alpha, pubmed-meshheading:19362162-Response Elements, pubmed-meshheading:19362162-Up-Regulation
pubmed:year
2009
pubmed:articleTitle
Differential regulation of the human versus the mouse apolipoprotein AV gene by PPARalpha. Implications for the study of pharmaceutical modifiers of hypertriglyceridemia in mice.
pubmed:affiliation
INSERM UMR-S, Hôpital de la Pitié, Paris, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't