Transcriptional Regulation of Cellular Retinol-Binding Protein, Type II Gene Expression in Small Intestine by Dietary Fat

Abstract

We have previously demonstrated that dietary fat, especially unsaturated fatty acids, induces cellular retinol-binding protein, type II (CRBPII) gene expression in rat jejunum. In the present study, we showed that feeding a high-fat diet caused parallel increases in jejunal CRBPII mRNA and CRBPII pre-mRNA levels. Nuclear run-on assay also revealed that this increase of CRBPII mRNA level by high-fat diet was, at least in part, triggered at a transcription level. Moreover, peroxisome proliferator-activated receptor alpha (PPARα) mRNA level was also increased in the jejunum by high-fat diet. Gel shift assay showed that the binding activity of rat jejunal nuclear protein to the nuclear receptor response elements located in the rat CRBPII gene (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 PPARα protein. Also PPARα-retinoid X receptor alpha (RXRα) heterodimer was capable of binding to the CRBPII-RXRE and RE3 elements and these binding activities were enhanced by addition of some PPARα ligands in the gel shift assay. Taken together, these studies suggest that dietary fatty acids may lead to induction of CRBPII gene transcription through increases of PPARα as well as its ligand levels.