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Elucidation of the mechanism involved in energy metabolic regulation by heparan sulfate

Research Project

Project/Area Number 22590296
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionAichi Medical University

Principal Investigator

NAGAI Naoko  愛知医科大学, 分子医科学研究所, 助教 (00367799)

Co-Investigator(Kenkyū-buntansha) KIMATA Koji  愛知医科大学, 名誉教授 (10022641)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords糖鎖生物学 / 代謝 / ヘパラン硫酸 / Hs6st2 / FGF21 / 褐色脂肪細胞 / Ucp1 / エネルギー代謝 / 糖鎖 / 甲状腺ホルモン / 甲状腺 / 褐色脂肪組織
Research Abstract

Heparan sulfate (HS) is a glycosaminoglycan chain which localizes extracellulary where it plays important roles in various biological processes. Heparan sulfate 6-O-sulfotransferase-2 (Hs6st2) is one of the enzymes that add sulfate groups to HS. Here we report that male Hs6st2 knockout mice showed reduced energy metabolism. Thus, 6-O-sulfation in HS seems to play an important role in mediating energy metabolism and alteration of the HS composition may result in metabolic syndrome phenotypes. Heparan sulfate 6-O-sulfation was reduced in brown adipose tissue, a major tissue regulating energy metabolism. When cultures of brown adipocytes from wild type and Hs6st2 knockout mice isolated and differentiated in vitro were treated with FGF21, downstream signaling was reduced. The serum level of thyroid stimulating hormone was significantly higher, and that of thyroxin was lower in the knockout mice, suggesting hypothyroid phenotype.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (13 results)

All 2013 2011 2010 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (4 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Involvement of heparan sulfate 6-O-sulfation in regulation of energy metabolism and alteration of thyroid hormone levels in male mice.2013

    • Author(s)
      Nagai N, Habuchi H, Sugaya N, Nakamura M, Imamura T, Watanabe H, Kimata K.
    • Journal Title

      Glycobiology

      Volume: 23 Issue: 8 Pages: 980-992

    • DOI

      10.1093/glycob/cwt037

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heparan sulfate 6-O-sulfotransferase isoform-d ependent regulatory effects of heparin on the activities of various proteases in mast cells a nd the biosynthesis of 6-O-sulfated heparin.2013

    • Author(s)
      Anower-E-Khuda MF, Habuchi H, Nagai N, Habuchi O, Yokochi T, Kimata K.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 288 Issue: 6 Pages: 3705-3717

    • DOI

      10.1074/jbc.m112.416651

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suzuki M, Imamura, T Sulfated glycosaminoglycans are required for specific and sensitive fibroblast growth factor (FGF) 19 signaling via FGF receptor 4 and betaKlotho2011

    • Author(s)
      Nakamura M, Uehara Y, Asada M, Honda E, Nagai,N, Kimata K
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 286 Issue: 30 Pages: 26418-26423

    • DOI

      10.1074/jbc.m111.251140

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell surface heparan sulfate chains regulate local reception of FGF signaling in the mouse embryo.2011

    • Author(s)
      Shimokawa K, Kimura-Yoshida C, Nagai N, Mukai K, Matsubara K, Watanabe H, Matsuda Y, Mochida K, Matsuo I
    • Journal Title

      Developmental Cell

      Volume: 21 Pages: 257-2721

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell surface heparin sulfate chains regulate local reception of FGF signaling in the mouse embryo2011

    • Author(s)
      下川佳世
    • Journal Title

      Developmental Cell

      Volume: 21 Issue: 2 Pages: 257-272

    • DOI

      10.1016/j.devcel.2011.06.027

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chondroitin Sulfate Synthase-2/Chondroitin Polymerizing Factor Has Two Variants with Distinct Function2010

    • Author(s)
      Hiroyasu Ogawa, et al.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 285 Pages: 34155-34167

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Increased body weight in heparan sulfate6-O-sulfotransferase (Hs6st2) knockout mice2011

    • Author(s)
      永井尚子
    • Organizer
      第71回岡崎コンファレンス
    • Place of Presentation
      岡崎コンファレンスセンター(愛知)
    • Year and Date
      2011-10-13
    • Related Report
      2012 Final Research Report
  • [Presentation] Increased body weight in heparan sulfate 6-O-sulfotransferase (Hs6st2) knockout mice2011

    • Author(s)
      永井尚子
    • Organizer
      第71回岡崎コンファレンス
    • Place of Presentation
      岡崎コンファレンスセンター
    • Year and Date
      2011-10-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Altered Energy Expenditure in Heparan Sulfate6-O-sulfotransferase-2 knockout mice2010

    • Author(s)
      永井尚子
    • Organizer
      第28回内藤コンファレンス
    • Place of Presentation
      湘南国際村センター(神奈川県)
    • Year and Date
      2010-07-28
    • Related Report
      2012 Final Research Report
  • [Presentation] Altered Energy Expenditure in Heparan Sulfate 6-O-sulfotransferase-2 knockout mice2010

    • Author(s)
      永井尚子
    • Organizer
      第28回内藤コンファレンス
    • Place of Presentation
      湘南国際村センター(神奈川県)
    • Year and Date
      2010-07-28
    • Related Report
      2010 Annual Research Report
  • [Book] 生物機能モデルと新しいリソース・リサーチツール2011

    • Author(s)
      永井尚子
    • Publisher
      木全弘治株式会社エル・アイ・シー
    • Related Report
      2012 Final Research Report
  • [Book] 生物機能モデルと新しいリソース・リサーチツール2011

    • Author(s)
      永井尚子
    • Publisher
      株式会社 エル・アイ・シー
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.aichi-med-u.ac.jp/su10/su1009/index.html

    • Related Report
      2012 Final Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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