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Induction of 1-acylglycerophosphocholine acyltransferase genes by fibrates in the liver of rats.
MedLine Citation:
PMID:  22975502     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The effect of fibrates (clofibric acid, bezafibrate and fenofibrate) on the gene expression and activity of 1-acylglycerophosphocholine acyltransferase (LPCAT) was investigated. The administration of 0.1% (w/w) clofibric acid, bezafibrate or fenofibrate in diet for 14 d to rats induced LPCAT activity in hepatic microsomes in the following order: fenofibrate>bezafibrate>clofibric acid. The LPCAT induced by fenofibrate preferred to arachidonoyl-CoA and linoleoyl-CoA to a greater extent than did LPCAT in control microsomes. The treatment with the fibrates resulted in upregulation of the relative expression of mRNAs encoding LPCAT3 and LPCAT4 in the following order: fenofibrate>bezafibrate>clofibric acid. The administration of fibrates did not change the expression of genes encoding either LPCAT1 or LPCAT2. The treatment with fibrates elevated relative levels of both mRNAs encoding Δ6 desaturase (Fads2) and Δ5 desaturase (Fads1) in the order of fenofibrate>bezafibrate>clofibric acid, and the extent of the increase in the level of Δ6 desaturase mRNA was greater than that of Δ5 desaturase. Fatty acid profile in hepatic phosphatidylcholine (PC) was significantly changed by the treatments with fibrates. These results suggest (i) that fibrates induce LPCAT activity in hepatic microsomes by elevating the expression of genes encoding LPCAT3 and LPCAT4, (ii) that the changes in fatty acid profile of hepatic PC are, in part, due to the elevated expression of two isoforms, LPCAT3 and LPCAT4, and (iii) that the ability of fibrates to induce these changes are in the order of fenofibrate>bezafibrate>clofibric acid.
Authors:
Tohru Yamazaki; Michiko Wakabayashi; Erika Ikeda; Shizuyo Tanaka; Takeshi Sakamoto; Atsushi Mitsumoto; Naomi Kudo; Yoichi Kawashima
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  35     ISSN:  1347-5215     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2012  
Date Detail:
Created Date:  2012-09-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1509-15     Citation Subset:  IM    
Affiliation:
Faculty of Pharmaceutical Sciences, Josai University.
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