Differential induction of stearoyl-CoA desaturase and acyl-CoA oxidase genes by fibrates in HepG2 cells.
We studied whether two typical effects of fibrates, induction of stearoyl-CoA desaturase (EC 1.14.99.5) and peroxisome proliferation, are related. The effect of bezafibrate on the activity and mRNA of stearoyl-CoA desaturase and acyl-CoA oxidase in the liver and epididymal white adipose tissue of male Sprague-Dawley rats was determined. The same parameters were measured in HepG2 cells, a cell line resistant to peroxisome proliferation, following incubation with ciprofibrate. Bezafibrate increased the hepatic mRNA levels (14.5-fold on day 7) and activity (9.3-fold on day 15) of acyl-CoA oxidase. Stearoyl-CoA desaturase mRNA levels were transiently increased (2.7-fold on day 7), while its activity remained increased at the end of the treatment (2.4-fold). In white adipose tissue, bezafibrate increased the mRNA (5-fold) and activity (1.9-fold) of acyl-CoA oxidase, while stearoyl-CoA desaturase was not modified. Ciprofibrate addition to HepG2 cells cultured in 7% fetal bovine serum (FBS) only increased the stearoyl-CoA desaturase mRNA (1.9-fold). When cells were cultured in 0.5% FBS, ciprofibrate increased acyl-CoA oxidase mRNA (2.2-fold), while the increase in stearoyl-CoA desaturase mRNA was identical (1.9-fold). Further, its activity was also increased (1.5-fold). Incubation of HepG2 cells in the presence of cycloheximide did not alter the capacity of ciprofibrate to induce stearoyl-CoA desaturase mRNA, whereas the presence of actinomycin abolished the induction. In addition, preincubation of HepG2 cells with ciprofibrate increased the rate of stearoyl-CoA desaturase mRNA degradation. The results presented in this study suggest that fibrates induce stearoyl-CoA desaturase activity and mRNA levels independently of peroxisome proliferation.
Rodríguez
C
C
Unidad de Farmacología y Farmacognosia, Facultad de Farmacia, Universidad de Barcelona, 08028, Barcelona, Spain.
Cabrero
A
A
Roglans
N
N
Adzet
T
T
Sánchez
R M
RM
Vázquez
M
M
Ciudad
C J
CJ
Laguna
J C
JC
D042962:Acyl-CoA Oxidase; D000273:Adipose Tissue / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D003470:Culture Media / Q000032:analysis; D004790:Enzyme Induction / Q000187:drug effects; D058607:Fibric Acids; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D003470:Culture Media; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D002995:Clofibric Acid; D010088:Oxidoreductases; D013230:Stearoyl-CoA Desaturase; D042962:Acyl-CoA Oxidase; C019304:ciprofibrate; D001629:Bezafibrate