Transcriptional regulation of cellular retinol-binding protein, type II gene expression in small intestine by dietary fat

We have previously demonstrated that dietary fat, especially unsaturated fa tty acids, induces cellular retinol-binding protein, type II (CRBPII) gene expression in rat jejunum. In the present study, we showed that feeding a h igh-fat diet caused parallel increases in jejunal CRBPII mRNA and CRBPII pr e-mRNA levels. Nuclear run-on assay also revealed that this increase of CRB PII mRNA level by high-fat diet was, at least in part, triggered at a trans cription level. Moreover, peroxisome proliferator-activated receptor alpha (PPAR alpha) mRNA level was also increased in the jejunum by high-fat diet. Gel shift assay showed that the binding activity of rat jejunal nuclear pr otein to the nuclear receptor response elements located in the rat CRBPII g ene (RXRE and RE3) was greater in rats fed high-fat diet than in those fed fat-free diet and were enhanced by addition of bacterially expressed PPAR a lpha protein. Also PPAR alpha-retinoid X receptor alpha (RXR alpha) heterod imer was capable of binding to the CRBPII-RXRE and RE3 elements and these b inding activities were enhanced by addition of some PPAR alpha ligands in t he gel shift assay. Taken together, these studies suggest that dietary fatt y acids may lead to induction of CRBPII gene transcription through increase s of PPAR alpha as well as its ligand levels. (C) 1999 Academic Press.