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Regulation of vitamin A metabolism-related gene expression

Published online by Cambridge University Press:  09 March 2007

Sachiko Takase
Affiliation:
Department of Nutrition, Siebold University of Nagasaki, Nagasaki 851-2195, Japan
Kazuhito Suruga
Affiliation:
School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
Toshinao Goda*
Affiliation:
School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
*
*Corresponding author: Toshinao Goda, Laboratory of Nutritional Physiology, Department of Nutrition, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka-city, Shizuoka 422-8526, Japan, tel 81 54 264 5533, fax 81 54 264 5565, email gouda@fns1.u-shizuoka-ken.ac.jp
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Abstract

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Cellular retinol-binding protein, type II (CRBPII) is abundantly expressed in the small intestinal epithelial cells and plays a pivotal role in intestinal absorption and metabolism of retinol and β-carotene. In the 5′-flanking 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 been identified as putative binding sites for a heterodimer of peroxisome proliferator-activated receptor (PPAR) and retinoid X-receptor (RXR). We found 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, dietary fat (especially unsaturated fatty acids) has been shown to induce CRBPII gene expression in the jejunum. Nuclear run-on assays revealed that this increase of CRBPII mRNA levels by a high-fat diet was the result of the induction of the gene transcription through the rise in PPARα expression level as well as the increase in its ligand levels. Electrophoretic mobility shift assay using the DR-1 type cis-elements of CRBP II gene showed that PPARα-RXRα heterodimer was capable of binding to these elements, 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 diet. We also found that the expression of PPARδ was rather reduced by dietary fat. Thus, CRBPII gene expression is regulated predominantly by dietary fatty acids.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2000

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