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Integrative Medicice Focused on the Receptor Biniding Molecule for Obesity and Metabolic Syndrome

Research Project

Project/Area Number 16K19558
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Endocrinology
Research InstitutionYokohama City University

Principal Investigator

Kengo AZUSHIMA  横浜市立大学, 医学研究科, 客員研究員 (00760381)

Research Collaborator TAMURA Kouichi  
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords脂肪細胞 / 骨格筋 / インスリン抵抗性 / 肥満症 / 受容体 / レニン-アンジオテンシン系 / 脂肪組織 / 肥満 / 内科 / メタボリック症候群 / 統合医療
Outline of Final Research Achievements

Angiotensin II type 1 receptor (AT1R) is a major player in the signal transduction of renin-angiotensin system, and the overactivation of this signaling contributes to the progression of visceral obesity. AT1R-associated protein (ATRAP) promotes AT1R internalization along with the suppression of overactivation of tissue AT1R signaling. We demonstrated that the enhancement of ATRAP in adipose tissue ameliorated high-fat diet-induced visceral obesity and insulin resistance via the attenuation of overactivated AT1R signaling and adipose inflammation. Furthermore, we revealed that low-dose angiotensin II administration could promote the insulin resistance even in a lean type, and this finding was mainly caused by the dysfunction of glucose uptake in skeletal muscle due to increased oxidative stress. The enhancement of ATRAP in skeletal muscle ameliorated this insulin resistance in a lean type via the attenuation of overactivated AT1R signaling and oxidative stress in skeletal muscle.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results) Remarks (5 results)

  • [Int'l Joint Research] Duke-NUS Medical School(シンガポール)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Angiotensin II Type 1 Receptor-associated Protein Inhibits Angiotensin II-induced Insulin Resistance with Suppression of Oxidative Stress in Skeletal Muscle Tissue2018

    • Author(s)
      Ohki Kohji、Wakui Hiromichi、Kishio Nozomu、Azushima Kengo、Uneda Kazushi、Haku Sona、Kobayashi Ryu、Haruhara Kotaro、Kinguchi Sho、Yamaji Takahiro、Yamada Takayuki、Minegishi Shintaro、Ishigami Tomoaki、Toya Yoshiyuki、Yamashita Akio、Imajo Kento、Nakajima Atsushi、Kato Ikuma、Ohashi Kenichi、Tamura Kouichi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2846-2846

    • DOI

      10.1038/s41598-018-21270-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ATRAP Expression in Brown Adipose Tissue Does Not Influence the Development of Diet-Induced Metabolic Disorders in Mice2017

    • Author(s)
      Wakui H, Ohki K, Azushima K, Uneda K, Haku S, Kobayashi R, Haruhara K, Kinguchi S, Matsuda M, Ohsawa M, Maeda A, Minegishi S, Ishigami T, Toya Y, Yamashita A, Umemura S, Tamura K
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 3 Pages: 676-676

    • DOI

      10.3390/ijms18030676

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adipocyte-Specific Enhancement of Angiotensin II Type 1 Receptor-Associated Protein Ameliorates Diet-Induced Visceral Obesity and Insulin Resistance.2017

    • Author(s)
      Azushima K, Ohki K, Wakui H, Uneda K, Haku S, Kobayashi R, Haruhara K, Kinguchi S, Matsuda M, Maeda A, Toya Y, Yamashita A, Umemura S, Tamura K.
    • Journal Title

      J Am Heart Assoc.

      Volume: 6 Issue: 3

    • DOI

      10.1161/jaha.116.004488

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Adipocyte angiotensin II type 1 receptor (AT1R)-associated protein prevents diet-induced visceral obesity and insulin resistance through the suppression of overactivated tissue AT1R signaling2018

    • Author(s)
      Azushima K, Wakui H, Uneda K, Kobayashi R, Haku S, Ohki K, Haruhara K, Kinguchi S, Yamashita A, Umemura S, Tamura K
    • Organizer
      ISN Frontiers Meetings 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Protective Role of Angiotensin II Type 1 Receptor Associated Protein in Metabolic Disorders2018

    • Author(s)
      Kohji Ohki, Hiromichi Wakui, Kengo Azushima, Kazushi Uneda, Ryu kobayashi, Sona Haku, Kotaro Haruhara, Sho Kinguchi, Takayuki Yamada, Takahiro Yamaji, Nozomu Kishio, Kento Imajo Atsushi Nakajima, Akio Yamashita, Yoshiyuki Toya and Kouichi Tamura
    • Organizer
      ISN Frontiers Meetings 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Adipose tissue angiotensin II type 1 receptor-associated protein prevents diet-induced visceral obesity and insulin resistance2017

    • Author(s)
      Azushima K, Ohki K, Wakui H, Tamura K
    • Organizer
      13th Asian-Pacific Congress of Hypertension
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Renin-angiotensin system and metabolic diseases2017

    • Author(s)
      Azushima K
    • Organizer
      Satellite Interstellar Initiative at A*STAR
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mouse models of diabetic nephropathy2017

    • Author(s)
      Azushima K
    • Organizer
      4th Next Generation Kidney Research Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アディポネクチンプロモーター制御下1型アンジオテンシンII受容体結合因子(ATRAP)高発現マウスにおける慢性アンジオテンシンII刺激によるインスリン抵抗性の検討2017

    • Author(s)
      大城 光二,涌井 広道,大澤 正人,小豆島 健護,白 善雅,畝田 一司,小林 竜,春原 浩太郎,金口 翔,山田 貴之,山地 孝拡,岸尾 望,田村 功一
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖脂質代謝障害における1型アンジオテンシンII受容体結合蛋白ATRAPの機能的意義2017

    • Author(s)
      大城 光二,涌井広道, 大澤正人, 小豆島健護, 畝田一司, 小林竜, 白善雅, 春原浩太郎, 金口翔, 山田貴之, 山地孝拡, 松田美由紀, 岸尾望, 今城健人, 中島淳, 山下暁朗, 戸谷義幸, 田村功一
    • Organizer
      第21回心血管内分泌代謝学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪組織におけるアンジオテンシン受容体結合因子(ATRAP/Agtrap)の高発現は食餌性肥満およびインスリン抵抗性の増悪を抑制する2016

    • Author(s)
      小豆島 健護
    • Organizer
      第39回日本高血圧学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Adipose tissue ATRAP (angiotensin II type 1 receptor-associated protein) prevents diet-induced visceral obesity and insulin resistance via the alternation of adipose GLUT4 expression2016

    • Author(s)
      Kengo Azushima
    • Organizer
      The ISH 2016 satellite symposium, Renin-angiotensin-aldosterone system (RAAS)
    • Place of Presentation
      コングレススクエア日本橋(東京都中央区)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] ISN FRONTIERS MEETINGS 2018にて小豆島博士がTravel Grantを受賞

    • URL

      http://www.yokohama-medicine.org/news/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 循環器・腎臓・高血圧内科学の大城光二医師が、やせ型インスリン抵抗性と骨格筋との関わりについて発表

    • URL

      http://www.yokohama-medicine.org/news/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 小豆島博士が13th APCHにてYIAを獲得

    • URL

      http://www.yokohama-medicine.org/news/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 小豆島健護博士が次世代腎研究アカデミー第4回学術集会にて招待講演を行い,表彰されました!

    • URL

      http://www.yokohama-medicine.org/news/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 循環器・腎臓内科学の小豆島健護博士が, 脂肪細胞機能制御による生活習慣病の新規治療の可能性を発表

    • URL

      http://www.yokohama-medicine.org/news/

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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