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-C oA 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 ma le 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 level s (14.5-fold on day 7) and activity (9.3-fold on day 15) of acyl-CoA oxidas e. Stearoyl-CoA desaturase mRNA levels were transiently increased (2.7-fold on day 7)), while its activity remained increased at the end of the treatm ent (2.4-fold). In whits adipose tissue, bezafibrate increased the mRNA (5- fold) and activity (1.9-fold) of acyl-CoA oxidase, while stearoyl-CoA desat urase 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 acy l-CoA oxidase mRNA (2.2-fold), while the increase in stearoyl-CoA desaturas e 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 no t 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 stear oyl-CoA desaturase mRNA degradation. The results presented in this study su ggest that fibrates induce stearoyl-CoA desaturase activity and mRNA levels independently of peroxisome proliferation. (C) 2001 Elsevier Science Inc. All rights reserved.