Clofibrate causes an upregulation of PPAR-{alpha} target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs.
This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-alpha and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-alpha target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs (P < 0.05). mRNA concentrations of sterol regulatory element-binding proteins (SREBP)-1 and -2, insulin-induced genes (Insig)-1 and Insig-2, and the SREBP target genes acetyl-CoA carboxylase, 3-methyl-3-hydroxyglutaryl-CoA reductase, and low-density lipoprotein receptor in liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-alpha in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-alpha activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs.
Luci
Sebastian
S
Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhalden-Strasse 26, D-06108 Halle/Saale, Germany.
Giemsa
Beatrice
B
Kluge
Holger
H
Eder
Klaus
K
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000235:genetics; D016633:Apolipoprotein A-II / Q000096:biosynthesis / Q000235:genetics; D053305:Apolipoprotein C-III / Q000096:biosynthesis / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics*; D013552:Swine; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053305:Apolipoprotein C-III; D002352:Carrier Proteins; D008074:Lipoproteins; D047493:PPAR alpha; D012333:RNA, Messenger; D051779:Sterol Regulatory Element Binding Proteins; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol; D002994:Clofibrate; D020155:3-Hydroxybutyric Acid