Increase in hepatic expression of SREBP-2 by gemfibrozil administration to rats.
It is well known that gemfibrozil increases the biliary output of cholesterol and phospholipids, but we have little knowledge about the impact these changes have on liver cholesterol and phospholipid biosynthetic pathways. In the present study, no changes were detected in liver lipids and CTP:phosphocholine cytidylyltransferase after gemfibrozil administration to rats. On the contrary, 3-hydroxy-3-methylglutaryl-CoA reductase mRNA (9.9-fold) and Rd activity (16.7-fold) and phosphatidate phosphohydrolase activity (1.7-fold) increased, while plasma apo B-cholesterol (40%) and triglyceride (43%) levels decreased. As a part of a compensatory homeostatic response, we report for the first time that gemfibrozil administration to rats increased the hepatic sterol regulatory element binding protein-2 (SREBP-2) mRNA (2.9-fold) and mature protein (2.2-fold) levels. An early increase in the transcriptional activity of SREBP-2 elicited by gemfibrozil administration might be responsible for the observed changes in HMG-CoA reductase, phosphatidate phosphohydrolase, and SREBP-2 expression.
Roglans
N
N
Unidad de Farmacologia y Famacognosia, Facultad de Farmacia, Universidad de Barcelona, Nucleo Universitario de Pedralbes, 08028, Barcelona, Spain.
Peris
C
C
Verd
J C
JC
Alegret
M
M
Vázquez
M
M
Sánchez
R M
RM
Laguna
J C
JC
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015248:Gemfibrozil / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D015248:Gemfibrozil