EVIDENCE FOR TRANSCRIPTIONAL INDUCTION OF THE LIVER FATTY-ACID-BINDING-PROTEIN GENE BY BEZAFIBRATE IN THE SMALL-INTESTINE

The effect of bezafibrate on cytosolic fatty-acid-binding-protein (FAB Pc) production along the small intestine has been investigated in mice . This drug increased the intestinal fatty-acid-binding-protein (I-FAB Pc) and liver fatty-acid-binding-protein (L-FABPc) mRNA levels in the duodenum. The extents of induction in the duodenum and in the liver ar e similar. However, the degree of stimulation gradually decreases alon g the length of the gut, no effect being found in the ileum. An effici ent absorption of this drug as early as the proximal part of the small intestine may explain this phenomenon. The L-FABPc gene is silent in terminal ileum of mice, but a direct infusion of bezafibrate into the ileum switches it on. We used this original model to follow the time c ourse of induction of the L-FABPc gene by bezafibrate. L-FABPc mRNA wa s first detected 4 h after fibrate infusion, reached a maximum level a t 16 h and subsequently decreased at 24 h. This induction was totally blocked by cycloheximide. Sunflower oil also caused small increases in the L-FABPc mRNA levels. The transcriptional origin of the induction triggered both by bezafibrate and sunflower oil was demonstrated by ru n-on assays. These data indicate that (a) the transcription of the L-F ABPc gene is induced by bezafibrate via de novo protein synthesis and (b) components of sunflower oil can transcriptionally activate the L-F ABPc gene. Our results also demonstrate that the mouse terminal ileum is a useful system for studying the regulation of L-FABPc gene express ion both in vivo and in vitro.