Differential induction of stearoyl-CoA desaturase and acyl-CoA oxidase genes by fibrates in HepG2 cells.

Biochem Pharmacol 2001 Feb 1;61(3):357-364

Rodriguez C, Cabrero A, Roglans N, Adzet T, Sanchez RM, Vazquez M, Ciudad CJ, Laguna JC

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.

PMID: 11172741