| Project/Area Number |
15590213
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | University of Shizuoka |
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Principal Investigator |
GODA Toshinao University of Shizuoka, School of Food and Nutritional Sciences, Department of Nutrition, Associate Professor, 食品栄養科学部, 助教授 (70195923)
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| Co-Investigator(Kenkyū-buntansha) |
SURUGA Kazuhito School of Food and Nutritional Sciences, Department of Nutrition, Instructor, 食品栄養科学部, 助手 (70315852)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | intestine / nuclear receptor / transcription / fatty acid / retinoic acid / phosphorylation / development / proteomics / フルクトース / 甲状腺ホルモン / 脱リン酸化 |
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| Research Abstract |
1. Transcription factors involved in the expression of digestion/absorption-related genes during development: In the perinatal period, the expression of cellular retinol-binding protein, type II (CRBPII) was abruptly elevated in rat small intestine. This was accompanied by a coordinated and marked expression of RXR α and HNF-4 in the nuclei of villus cells. The gene expression of RALDH1 and RALDH2 involved in the generation of retinoic acid was elevated in the liver and small intestine just before birth. The organ culture of the small intestine obtained just before birth showed an induction of CRBPII gene in the presence of RXR α ligand.
2. The expression of transcription factors related to digestion and absorption in the small intestine and the modulation induced by phosphorylation.: Rats fed a high-fat diet showed a greater expression of CRBPII from the base to the tip of the villi. In these animals, the gene expression of PPAR α and HNF-4 were coordinately elevated, while that of PPAR δ was reduced. The proteomics analysis of PPAR δ target genes using C2BBe1 revealed that HMG-CoA synthase and glutathione S transferase were induced by PPAR δ ligand. The forskolin-induced phosphorylation of HNF-4 caused the reduction of the binding activity of HNF-4 to the DR-1 element on the CRBPII gene promoter. These results suggest that the basic expression of CRBPII is maintained by HNF-4, and its level is modulated by RXR α ligand.
3. Mechanism involved in the diurnal variation of the expression of digestion/absorption-related genes: The expression of CRBPII in rat jejunum showed a diurnal variation at a transcriptional level, which depended on the dietary fat content, and lost in rats fed a fat-free diet. These results suggest that dietary fatty acids may play a role in the diet-induced diurnal variation of CRBPII gene expression.
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