Regulation of vitamin A metabolism-related gene expression

Cellular retinol-binding protein, type II (CRBPII) is abundantly expressed in the small intestinal epithelial cells and plays a pivotal role in intest inal absorption and metabolism of retinol and beta -carotene. In the 5'-fla nking region of rat CRBPII gene, two DR-1 type elements which consist of a direct repeat of the AGGTCA-like motif spaced by a single nucleotide have b een identified as putative binding sites for a heterodimer of peroxisome pr oliferator-activated receptor (PPAR) and retinoid X-receptor (RXR). We foun d that CRBPII levels were elevated in the residual jejunal segment of rats subjected to jejunal bypass operation, where a concomitant increase in the apoprotein B levels occurred. This result suggested that CRBPII expression was enhanced by a condition where fat absorption was stimulated. Indeed, di etary fat (especially unsaturated fatty acids) has been shown to induce CRB PII gene expression in the jejunum. Nuclear ran-on assays revealed that thi s increase of CRBPII mRNA levels by a high-fat diet was the result of the i nduction of the gene transcription through the rise in PPAR alpha expressio n level as well as the increase in its ligand levels. Electrophoretic mobil ity shift assay using the DR-1 type cis-elements of CRBP II gene showed tha t PPAR alpha -RXR alpha heterodimer was capable of binding to these element s, and that nuclear extracts from the jejunum of rats fed the high-fat diet gave greater density of retarded bands than those of rats fed a fat-free d iet. We also found that the expression of PPAR delta was rather reduced by dietary fat. Thus, CRBPII gene expression is regulated predominantly by die tary fatty acids.