| Project/Area Number |
12671131
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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 |
Metabolomics
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| Research Institution | National Institute of Health and Nutrition |
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Principal Investigator |
EZAKI Osamu National Institute of Health and Nutrition, Divesion of Clinical Nutrition, Division Director, 国立健康・栄養研究所・生活習慣病研究部, 部長 (90191923)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | GLUT4 / Cis-element / Insulin resistance / High-fat diet / Adipose tissue / Transgenic mice |
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| Research Abstract |
GLUT4, the insulin responsive-glucose transporter, mediates the rate limiting step of glucose metabolism in skeletal muscles and adipose tissues. High-fat feeding downregulates GLUT4 mRNA and decreases in insulin-stimulated glucose uptake in white adipose tissues (WAT). By using 5 -deleted mouse GLUT4 minigene transgenic mice, we have demonstrated that adipocyte specific element (s) of mouse GLUT4 are located within 45 bps between -551 and -506 relative to transcription initiation site, while high fat responsive element (s) is located within 150 bps between -701 and -551.DNase I footprinting analysis revealed that nuclear extract in WAT from both high-carbohydrate and high-fat diet fed mice protected the region from -705 to 682 (correspond to NF-1 site) and from -673 to 651 from DNase I digestion. This result showed that nuclear proteins bind to these regions regardless diet. Transgenic animal study indicated that mutation of NF-1 site near 701 abolished GLUT4 expression specially in white adipose tissues. These data suggest that a putative adipocyte specific enhancer binds both NF-1 and 45 bps between 551 and 506, while high-fat diet responsive enhancer binds 150 bps between 701 and 551 with some interaction to adipocyte specific enhancer.
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