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ROLE OF CALPAIN ON THE DIFFERENTIATION AND FUNCTION OF ADIPOCYTES

Research Project

Project/Area Number 13671209
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

YAJIMA Yukiko  Tokyo Metropolitan Organization for Medical Research, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, RESEARCHER, 研究員 (60090114)

Co-Investigator(Kenkyū-buntansha) SATO Mayumi  Tokyo Metropolitan Organization for Medical Research, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, 研究員 (50124459)
KUSUBATA Kaori  Tokyo Metropolitan Organization for Medical Research, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, 研究員 (80321884)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsCALPAIN / ADIPOCYTE DIFFERENTIATION / CALPASTATIN / INHIBITOR / INSULIN / GLUCOSE UPTAKE / GLUT4 / C / EBP / PPARγ / 3T3-L1 / ST-13
Research Abstract

Calpain is a calcium-activated non-lysosomal neutral thiol protease (EC 3.4.22.17) present in a wide variety of eukaryotic cells. Calpain is usually present as an inactive form and is activated by calcium ions and phospholipids. The activity of calpain is required during the mitotic clonal expansion phase of 3T3-L1 preadipocyte differentiation. We addressed that blocking calpain activity enhances the adipogenesis of adult primitive mesenchymal ST-13 preadipocytes, the differentiation of which using standard hormones does not require mitotic clonal expansion. We also examined whether a calpain blockade induces insulin resistance in mature ST-13 adipocytes. Exposing ST-13 preadipocytes to the calpain inhibitor, N-benzyloxycarbonyl-L-leucyl-L-leucinal or to the overexpression of calpastatin, a specific endogenous inhibitor of calpain, stimulated acquisition of the adipocyte phenotype. Overexpression of calpastatin in ST-13 adipocytes stimulated the expression of the adipocyte-specific CCAAT/enhancer-binding protein a (C/EBP α), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP-1) and the insulin signaling molecules, insulin receptor α, insulin-receptor substrates and GLUT4. However, insulin-stimulated glucose uptake was reduced by approximately 52%. These results suggest that calpain negatively regulates adipogenesis in adult primitive mesenchymal ST-13 preadipocytes in contrast to that of embryonic 3T3-L1 preadipocytes and is required for the insulin-stimulated glucose uptake in mature ST-13 adipocytes.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Sato M, Yajima Y, Kawashima S, Tanaka K, Kagechika H: "Synergistic Potentiation of Thiazolidinedione-Induced ST 13 Preadipocyte"Biochem Biophysi.Research Commun. 280. 646-651 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato, M., Tai, T., Nunoura, Y, Yajima Y., et al.: "Dehydro-trametenolic acid induces preadipocyte differentiation and sensitizes"Biol.Pharmaceut.Bull. 25. 81-86 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yajima, Y., Kawashima, S.: "Calpain function in the differentiation of mesenchymal stem cells"Biol.Chem. 383. 757-764 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 矢島由紀子, 佐藤眞友美, 川島誠一: "脂肪細胞の分化とその機能におけるカルパインの役割"内分泌・糖尿病科. 16. 81-89 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yajima Y, Sato M, Sumida M, Kawashima S: "Mechanism of adult primitive mesenchymal ST-13 preadipocyte differentiation"Endocrinology. 144. 2559-2565 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato M, Yajima Y, Kawashima S, Tanaka K, Kagechika H: "Synergistic Potentiation of Thiazolidinedione-Induced ST 13 Preadipocyte Differentiation by RAR Synergists^*1."Biochem Biophysi. Research Commun.. 280. 646-651 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato, M., Tai, T., Nunoura, Y., Yajima, Y., Kawashima, S., Tanaka, K.: "Dehydro-trametenolic acid induces preadipocyte differentiation and sensitizes animal models of non-insulin-dependent diabetes millitus to insulin."Biol.Pharmaceut.Bull.. 25. 81-86 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yajima, Y., Kawashima, S.: "Calpain function in the differentiation of mesenchymal stem cells."Biol.Chem.. 383. 757-764 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yajima Y, Sato M, Kawashima S: "Role of calpain on the differentiation and function of adipocytes."Endocrinology and Diabetes. 16. 81-89 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yajima Y, Sato M, Sumida M, Kawashima S.: "Mechanism of adult primitive mesenchymal ST-13 preadipocyte differentiation."Endocrinol.. 144. 2559-2565 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 矢島由紀子, 佐藤眞友美, 川島誠一: "脂肪細胞の分化とその機能におけるカルパインの役割"内分泌・糖尿病科. 16. 81-89 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yajima Y, Sato M, Sumida M, Kawashima S: "Mechanism of adult primitive mesenchymal ST-13 preadipocyte differentiation"Endocrinology. 144. 2559-2565 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato M, Tai T, Nunoura Y, Yajima Y, Kawashima S, Tanaka K: "Dehydro-trametenolic acid induces preadipocyte differentiation and sensitizes animal models of non-insulin-dependent diabetes millitus to insulin"Biol. Pharmaceut. Bull. 25. 81-86 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yajima Y, Kawashima S: "Calpain function in the differentiation of mesenchymal stem cells"Biol. Chem. 383. 757-764 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yajima Y, Sato M, Sumida M, Kawashima S: "Mechanism of adult primitive mesenchymal ST-13 preadipocyte differentiation"Endocrinol.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 矢島由紀子, 佐藤真友美, 川島誠一: "脂肪細胞の分化とその機能におけるカルパインの役割"内分泌・糖尿病科. 16(1). 81-89 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Yajima, S.Kawashima: "Calpain Function in the Differentiation of Mesenchymal Stem Cells"Biological Chemistry. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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