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Mechanism for down-regulation of GLUT4 by high-fat diet

Research Project

Project/Area Number 12671131
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionNational Institute of Health and Nutrition

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)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
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)
KeywordsGLUT4 / Cis-element / Insulin resistance / High-fat diet / Adipose tissue / Transgenic mice
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.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] N.Tsunoda, K.Maruyama, D.W.Cooke, D.M.Lane, O.Ezaki: "Localization of Exercise-and Denervation-Responsive Elements in the Mouse GLUT4 Gene"Biochemical and Biophysical Research Communications. 267. 744-751 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsunoda, N., Maruyama, K., Cooke, D. W., Lane, M. D. and Ezaki, O.: "Localization of exercise-and denervation-responsive elements in the mouse GLUT4 gene."Biochem. Biophys. Res. Commun.. 267. 744-751 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tuboyama-Kasaoka, N., Tsunoda, N., Maruyama, K., Takahashi, M., Kim, H., Cooke, D. W., Lane, M. D. and Ezaki, O.: "Overexpression of GLUT4 in mice causes up- regulation of UCP3 mRNA in skeletal muscle."Biochem. Biophys. Res. Commun.. 258. 187-193 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsuboyama-Kasaoka, N., Tsunoda, N., Maruyama, K., Takahashi, M., Kim, H., Ikemoto, S. and Ezaki, O.: "Up-regulation of uncoupling protein 3 (UCP3) mRNA by exercise traning and down-regulation of UCP3 by denervation in skeletal muscles."Biochem. Biophys. Res. Commun.. 247. 498-503 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N.Tsunoda, K.Maruyama, D.W.Cooke, D.W Lane, O.Ezaki: "Localization of Exercise-and Denervation-Responsive Elements in the Mouse GLUT4 Gene"Biochemical and Biophysical Research Communications. 267. 744-751 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Tsunoda,K.Maruyama,D.W.Cooke,D.M.Lane,O.Ezaki: "Localization of Exercise-and Denervation-Responsive Elements in the Mouse GLUT4 Gene"Biochemical and Biophysical Research Communications. 267. 744-751 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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