UP-REGULATION OF THE EXPRESSION OF THE GENE FOR LIVER FATTY-ACID-BINDING PROTEIN BY LONG-CHAIN FATTY-ACIDS

The role of fatty acids in the expression of the gene for liver fatty acid-binding protein (L-FABP) was investigated in the well-differentia ted FAO rat hepatoma cell line. Cells were maintained in serum-free me dium containing 40 mu M BSA/320 mu M oleate. Western blot analysis sho wed that oleate triggered an approx. 4-fold increase in the cytosolic L-FABP level in 16 h. Oleate specifically stimulated L-FABP mRNA in ti me-dependent and dose-dependent manners with a maximum 7-fold increase at 16 h in FAO cells, Preincubation of FAO cells with cycloheximide p revented the oleate-mediated induction of L-FABP mRNA, showing that pr otein synthesis was required for the action of fatty acids. Run-on tra nscription assays demonstrated that the control of L-FABP gene express ion by oleate was, at least in part, transcriptional. Palmitic acid, o leic acid, linoleic acid, linolenic acid and arachidonic acid were sim ilarly potent whereas octanoic acid was inefficient. This regulation w as also found in normal hepatocytes. Therefore long-chain fatty acids are strong inducers of L-FABP gene expression. FAO cells constitute a useful tool for studying the underlying mechanism of fatty acid action .