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Analysis of the role of the immunoproteasome in obesity and diabetes

Research Project

Project/Area Number 26461386
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionJichi Medical University

Principal Investigator

Kimura Hiroaki  自治医科大学, 医学部, 講師 (70593622)

Co-Investigator(Kenkyū-buntansha) 白砂 孔明  東京農業大学, 農学部, 助教 (20552780)
臼井 文武  自治医科大学, 医学部, 助教 (50585560)
渡邊 幸子  自治医科大学, 医学部, 助教 (80770619)
Co-Investigator(Renkei-kenkyūsha) TAKAHASHI Masafumi  自治医科大学, 医学部, 教授 (40296108)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsimmunoproteasome / obeisty / LMP7 / macrophages / inflammation / diabetes / 免疫プロテアソーム / 脂肪細胞 / 分化 / マクロファージ / M2 / 炎症 / 脂肪 / 肥満 / 糖尿病
Outline of Final Research Achievements

The pathogenic mechanism of inflammation in obesity is not fully understood. Low-molecular-mass polypeptide-7 (LMP7), a proteolytic subunit of the immunoproteasome, plays a critical role in the immune system, and has been involved in the pathogenesis of several autoimmune diseases. We investigated the role of LMP7 in high fat diet-induced obesity using LMP7-deficient mice. LMP7 deficiency decreased body weight gain and fat accumulation, suppressed macrophage infiltration in the adipose tissue, improved glucose sensitivity. LMP7 deficiency also suppressed adipogenesis, and increased gene expression of M2 macrophage markers in fat tissues. These findings demonstrate that LMP7 in both hematopoietic and non-hematopoietic cells contributes to the pathogenesis of obesity.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015 2014 Other

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 10 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) Remarks (1 results)

  • [Journal Article] Caspse-1 deficiency promotes high-fat diet-induced adipose tissue inflammation and the development of obesity.2016

    • Author(s)
      Kimura H, Karasawa T, Usui F, Kawashima A, Endo Y, Kobayashi M, Sadatomo A, Nakamura J, Iwasaki Y, T Yada,Tsutsui H, Kasahara T, Takahashi M.
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 311 Issue: 5 Pages: 881-890

    • DOI

      10.1152/ajpendo.00174.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NLRP3 reduces macrophage interleukin-10 production and enhances the susceptibility to doxorubicin-induced cardiotoxicity.2016

    • Author(s)
      Kobayashi M, Usui F, Karasawa T, Kawashima A, Kimura H, Mizushina Y, Shirasuna K, Mizukami H, Kasahara T, Hasebe N, Takahashi M.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 26489-26489

    • DOI

      10.1038/srep26489

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunoproteasome subunit LMP7 Deficiency Improves Obesity and Metabolic Disorders2015

    • Author(s)
      Kimura H, Usui F, Karasawa T, Kawashima A, Shirasuna K, Inoue Y, Komada T, Kobayashi M, Mizushina Y, Kasahara T, Suzuki K, Iwasaki Y, Yada T, Caturegli P, Takahashi M.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 15883-15883

    • DOI

      10.1038/srep15883

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] NLRP3 deficiency improves angiotensin II-induced hypertension but not fetal growth restriction during pregnancy.2015

    • Author(s)
      Shirasuna K, Karasawa T, Usui F, Kobayashi M, Komada T, Kimura A, Ohkuchi A, Taniguchi S, Takahashi M.
    • Journal Title

      Endocrinology

      Volume: 156 Issue: 11 Pages: 4281-4292

    • DOI

      10.1210/en.2015-1408

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of NLRP3 inflammasomes for rhabdomyolysis-induced acute kidney injury.2015

    • Author(s)
      Komada T, Usui F, Kawashima A, Kimura H, Karasawa T, Inoue Y, Kobayashi M, Mizushina Y, Kasahara T, Taniguchi S, Muto S, Nagata D, Takahashi M.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 10901-10901

    • DOI

      10.1038/srep10901

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oligomerized CARD16 Promotes Caspase-1 Assembly and IL-1β Processing2015

    • Author(s)
      Tadayoshi Karasawa, Akira Kawashima, Fumitake Usui, Hiroaki Kimura, Koumei Shirasuna, Yoshiyuki Inoue, Takanori Komada, Motoi Kobayashi, Yoshiko Mizushina, Junji Sagara, Masafumi Takahashi
    • Journal Title

      FEBS Open Bio

      Volume: 5 Issue: 1 Pages: 348-356

    • DOI

      10.1016/j.fob.2015.04.011

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] New insights into the function of the immunoproteasome in immune and non-immune cells.2015

    • Author(s)
      Kimura H, Caturegli P, Takahashi M, Suzuki K.
    • Journal Title

      Journal of Immunology Research

      Volume: 2015 Pages: 541984-541984

    • DOI

      10.1155/2015/541984

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NLRP3 protein deficiency exacerbates hyperoxia-induced lethality through Stat3 protein signaling independent of interleukin-1β2015

    • Author(s)
      Mizushina Y, Shirasuna K, Usui F, Karasawa T, Kawashima A, Kimura H, Kobayashi M, Komada T, Inoue Y, Mato N, Yamasawa H, Latz E, Iwakura Y, Kasahara T, Bando M, Sugiyama Y, Takahashi M
    • Journal Title

      J Biol Chem

      Volume: 290 Issue: 8 Pages: 5065-5077

    • DOI

      10.1074/jbc.m114.603217

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1β in macrophages2014

    • Author(s)
      Hara K, Shirasuna K, Usui F, Karasawa T, Mizushina Y, Kimura H, Kawashima A, Ohkuchi A, Matsuyama S, Kimura K, Takahashi M
    • Journal Title

      PLoS One

      Volume: 9 Issue: 12 Pages: 1-17

    • DOI

      10.1371/journal.pone.0113974

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammasome activation by mitochondrial oxidative stress in macrophages leads to the development of angiotensin II-induced aortic aneurysm2014

    • Author(s)
      Usui F, Shirasuna K, Kimura H, Tatsumi K, Kawashima A, Karasawa T, Yoshimura K, Aoki H, Tsutsui H, Noda T, Sagara J, Taniguchi S, Takahashi M
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 35 Issue: 1 Pages: 127-136

    • DOI

      10.1161/atvbaha.114.303763

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nanosilica-induced placental inflammation and pregnancy complications: Different roles of the inflammasome components NLRP3 and ASC.2014

    • Author(s)
      Shirasuna K, Usui F, Karasawa T, Kimura H, Kawashima A, Mizukami H, Ohkuchi A, Nishimura S, Sagara J, Noda T, Ozawa K, Taniguchi S, Takahashi M.
    • Journal Title

      Nanotoxicology

      Volume: 11 Pages: 1-14

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] NLRP3 Regulates Neutrophil Functions and Contributes to Hepatic Ischemia-Reperfusion Injury Independently of Inflammasomes.2014

    • Author(s)
      Inoue Y, Shirasuna K, Kimura H, Usui F, Kawashima A, Karasawa T, Tago K, Dezaki, Nishimura S, Sagara J, Noda T, IwakuraY, Hiroko Tsutsui H, Taniguchi S, Yanagisawa K, Yada T, Yasuda Y, Takahashi M.
    • Journal Title

      J Immunol

      Volume: 192(9) Issue: 9 Pages: 4342-4351

    • DOI

      10.4049/jimmunol.1302039

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 高脂肪食による肥満性炎症におけるCaspase-1の役割2017

    • Author(s)
      木村博昭、唐澤直義、笠原忠、高橋将文
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] New insights into the role of the immunoproteasome in inflammatory diseases.2017

    • Author(s)
      Hiroaki Kimura, Tadayoshi Karasawa, Tadasahi Kasahara, Patrizio Caturegli, Masafumi Takahashi.
    • Organizer
      第19回武田振興財団生命科学シンポジウム(慢性炎症:機序と制御)
    • Place of Presentation
      武田薬品研修所(大阪府吹田市)
    • Year and Date
      2017-01-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 高脂肪食誘導型肥満における免疫プロテアソーム(LMP7)の役割2016

    • Author(s)
      木村博昭 唐澤直義 川島晃 臼井文武 笠原忠 鈴木幸一 高橋将文
    • Organizer
      第37回日本炎症・再生医学会
    • Place of Presentation
      みやこメッセ(京都)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脂肪酸結晶によるNLRP3インフラマソームを介した炎症惹起機構の解析2016

    • Author(s)
      唐澤直義、臼井文武、川島晃、木村博昭、高橋将文
    • Organizer
      第37回日本炎症・再生医学会
    • Place of Presentation
      みやこメッセ(京都)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 横紋筋融解症による急性腎障害におけるNLRP3インフラマソームの役割2016

    • Author(s)
      高橋将文、駒田敬則、臼井文武、唐澤直義、川島晃、木村博昭
    • Organizer
      第37回日本炎症・再生医学会
    • Place of Presentation
      みやこメッセ(京都)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 高脂肪食による肥満・メタボリック病態における免疫プロテアソーム欠損の有益な効果2016

    • Author(s)
      木村博昭 臼井文武 唐澤直義 川島晃 笠原忠 鈴木幸一 岩崎有作 矢田俊彦 高橋将文
    • Organizer
      高脂肪食による肥満・メタボリック病態における免疫プロテアソーム欠損の有益な効果
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 免疫プロテアソーム欠損は高脂肪食による肥満を抑制する2015

    • Author(s)
      木村博昭、臼井文武、唐澤直義、川島晃、笠原忠、岩崎有作、矢田俊彦、高橋将文
    • Organizer
      第36回日本肥満学会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 横紋筋融解症による急性腎障害におけるNLRP3インフラマソームの役割2015

    • Author(s)
      臼井文武、駒田敬則、唐澤直義、川島晃、木村博昭、武藤重明、長田太助、高橋将文
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 脂質代謝異常におけるASCの役割2015

    • Author(s)
      唐澤直義、木村博昭、臼井文武、川島晃、高橋将文
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Research-status Report
  • [Presentation] カスパーゼ1ホモログ分子CARD16による新規炎症惹起機序の解析2014

    • Author(s)
      唐澤直義、川島晃、臼井文武、木村博昭、高橋将文
    • Organizer
      第35回日本炎症・再生医学会
    • Place of Presentation
      沖縄県名護市
    • Year and Date
      2014-07-01 – 2014-07-04
    • Related Report
      2014 Research-status Report
  • [Presentation] NLRP3はインフラマソーム非依存的に肝虚血再灌流障害を軽減する2014

    • Author(s)
      高橋将文、井上賢之、白砂孔明、臼井文武、川島晃、木村博昭
    • Organizer
      第35回日本炎症・再生医学会
    • Place of Presentation
      沖縄県名護市
    • Year and Date
      2014-07-01 – 2014-07-04
    • Related Report
      2014 Research-status Report
  • [Presentation] 大動脈瘤形成におけるNLRP3インフラマソームの役割の解明2014

    • Author(s)
      臼井文武、木村博昭、唐澤直義、川島晃、高橋将文
    • Organizer
      第35回日本炎症・再生医学会
    • Place of Presentation
      沖縄県名護市
    • Year and Date
      2014-07-01 – 2014-07-04
    • Related Report
      2014 Research-status Report
  • [Presentation] LMP7欠損マウスの甲状腺異常2014

    • Author(s)
      木村博昭、川島晃、鈴木幸一、岩間信太郎、Patrizio Caturegli、高橋将文。
    • Organizer
      第86回日本内分泌学会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Remarks] 自治医科大学炎症・免疫研究部HP

    • URL

      http://www.jichi.ac.jp/inflammation/

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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