Differential effects of PPAR alpha activators on induction of ectopic expression of tissue-specific fatty acid binding protein genes in the mouse liver

The effect of a potent peroxisome proliferator-activated receptor (PPAR) al pha activator Wy14,643 on tissue-specific expression of fatty acid binding (FABP) genes was studied. Wy14,643 immediately induced liver-, intestine- a nd FABP but not PPAR gamma -regulated adipose-FABP (or aP2) mRNAs in respec tive mouse tissues. Moreover, it gradually induced ectopic expression of he art- and adipose-FABP mRNAs to significant levels in the liver. However, ec topic expression was not induced in the liver of PPAR alpha -null mouse, in dicating an obligatory role of the receptor in the modulated expression. Am ong the four PPAR alpha activators examined, only Wy14,643 induced ectopica l expression of heart-FABP in the liver. Thus, tissue-specificity of the FA BP gene expression is not absolute and, with a potent activator, can be dis torted by PPAR alpha. (C) 2000 Elsevier Science Ltd. All rights reserved.