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2011 Fiscal Year Final Research Report

Role of CCR5 and CX3CR1 in the development of insulin resistance

Research Project

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Project/Area Number 22790854
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Metabolomics
Research InstitutionKanazawa University

Principal Investigator

OTA Tsuguhito  金沢大学, フロンティアサイエンス機構, 特任助教 (60397213)

Project Period (FY) 2010 – 2011
Keywords炎症 / インスリン抵抗性 / ケモカイン / 脂肪組織 / 肥満 / マクロファージ
Research Abstract

Monocyte chemoattractant protein-1(MCP-1) and its receptor CCR2 are pivotal for adipose tissue macrophage(ATM) recruitment and the development of insulin resistance. However, other chemokine systems may also play a role in these processes. In this study, we investigated the role of CCR5 in obesity-induced adipose tissue inflammation and insulin resistance. We analyzed expression levels of CCR5 and its ligands in white adipose tissue(WAT) of genetically(ob/ob) and high-fat(HF) diet-induced obese(DIO) mice. CCR5 and its ligands were markedly upregulated in WAT of DIO and ob/ob mice. Fluorescence-activated cell sorter analysis also revealed that DIO mice had a robust increase in CCR5+cells within ATMs compared with chow-fed mice. Furthermore, Ccr5-/-mice were protected from insulin resistance, glucose intolerance, and hepatic steatosis induced by HF feeding. The effects of loss of CCR5 were related to both reduction of total ATM content and an M2 dominant shift in ATM polarization. Thus, CCR5 plays a critical role in ATM recruitment and polarization and subsequent development of insulin resistance.

  • Research Products

    (30 results)

All 2012 2011 2010 Other

All Journal Article (9 results) (of which Peer Reviewed: 6 results) Presentation (20 results) Remarks (1 results)

  • [Journal Article] Endoplasmic reticulum stress inhibits STAT3-dependent suppression of hepatic gluconeogenesis via dephosphorylation and deacetylation2012

    • Author(s)
      Kimura K, Yamada T, Matsumoto M, Kido Y, Hosooka T, Asahara S, Matsuda T, Ota T, Watanabe H, Sai Y, Miyamoto K, Kaneko S, Kasuga M, Inoue H
    • Journal Title

      Diabetes

      Volume: 61 Pages: 61-73

    • Peer Reviewed
  • [Journal Article] Inverse Correlation between Serum Levels of Selenoprotein P and Adiponectin in Patients with Type 2 Diabetes2012

    • Author(s)
      Misu H, Ishikura K, Kurita S, Takeshita Y, Ota T, Saito Y, Takahashi K, Kaneko S, Takamura T
    • Journal Title

      PLoS One

      Volume: 7 Pages: e34952

    • Peer Reviewed
  • [Journal Article] Different fatty acids inhibit apolipoprotein B100 secretion by different pathways : Unique roles for endoplasmic reticulum stress, ceramide, and autophagy2011

    • Author(s)
      Caviglia JM, Gayet C, Ota T, Hernandez-Ono A, Conlon DM, Jiang H, Fisher EA, Ginsberg HN
    • Journal Title

      J Lipid Res

      Volume: 52 Pages: 1636-1651

    • Peer Reviewed
  • [Journal Article] 脂肪肝の成因としての小胞体ストレスの意義,小胞体ストレスと疾患2011

    • Author(s)
      太田嗣人
    • Journal Title

      Bio Clinica

      Volume: 26(7) Pages: 28-32

  • [Journal Article] 慢性炎症とインスリン抵抗性をリンクするケモカインの役割,メタボリックシンドロームII(後篇)-メタボリックシンドロームの基礎-成因と病態/遺伝子・病態・標的分子の面から2011

    • Author(s)
      太田嗣人, 篁俊成
    • Journal Title

      ケモカイン最新医学

      Volume: 66(6) Pages: 192-204

  • [Journal Article] A liver-derived secretory protein, selenoprotein P, causes insulin resistance2010

    • Author(s)
      Misu H, Takamura T, Takayama H, Hayashi H, Matsuzawa-Nagata N, Kurita S, Ishikura K, Ando H, Takeshita Y, Ota T, Sakurai M, Yamashita T, Mizukoshi E, Honda M, Miyamoto K, Kubota T, Kubota N, Kadowaki T, Kim HJ, Lee IK, Minokoshi Y, Saito Y, Takahashi K, Yamada Y, Takakura N, Kaneko S
    • Journal Title

      Cell Metab

      Volume: 12 Pages: 483-495

    • Peer Reviewed
  • [Journal Article] Effect of pioglitazone on muscle sympathetic nerve activity in type 2 diabetes mellitus with alpha-glucosidase inhibitor2010

    • Author(s)
      Kobayashi D, Takamura M, Murai H, Usui S, Ikeda T, Inomata J, Takashima S, Kato T, Furusho H, Takeshita Y, Ota T, Takamura T, Kaneko S
    • Journal Title

      Auton Neurosci

      Volume: 158 Pages: 86-91

    • Peer Reviewed
  • [Journal Article] 肝疾患における血液,脂質一般検査生化学検査の臨床的意義2010

    • Author(s)
      太田嗣人, 篁俊成
    • Journal Title

      肝胆膵

      Volume: 60 Pages: 541-547

  • [Journal Article] CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status

    • Author(s)
      Kitade H, Sawamoto K, Nagashimada M, Inoue H, Yamamoto Y, Sai Y, Takamura T, Yamamoto H, Miyamoto K, Ginsberg HN, Mukaida N, Kaneko S, Ota T
    • Journal Title

      Diabetes IN PRESS

    • DOI

      doi:10.2337/db11-1506

    • Peer Reviewed
  • [Presentation] CCR5 ablation prevents insulin resistance induced by high-fat feeding or leptin deficiency2012

    • Author(s)
      Tsuguhito Ota, Hironori Kitade, Kazuki Sawamoto, Hiroshi Inoue, Toshinari Takamura, Naofumi Mukaida, Shuichi Kaneko
    • Organizer
      第16回国際動脈硬化シンポジウム
    • Place of Presentation
      シドニー(オーストラリア)
    • Year and Date
      2012-03-28
  • [Presentation] 肥満による炎症とインスリン抵抗性をリンクするCCR5の役割~脂肪組織マクロファージの量および質の調節への関与~2012

    • Author(s)
      太田嗣人1、澤本一樹1、北出紘規1、山本靖彦2、井上啓1、篁俊成3、山本博2、向田直史4、金子周一3
    • Organizer
      第26回日本糖尿病・肥満動物学会年次学術集会
    • Place of Presentation
      愛知県産業労働センター(愛知)
    • Year and Date
      2012-02-17
  • [Presentation] CCR5 plays a critical role in the inflammatory adipose tissue response to obesity by regulating both macrophage recruitment and M1/M2 status2011

    • Author(s)
      Tsuguhito Ota, Kazuki Sawamoto, Hironori Kitade, Yasuhiko Yamamoto, Hiroshi Inoue, Toshinari Takamura, Ken-ichi Miyamoto, Hiroshi Yamamoto Naofumi Mukaida, Shuichi Kaneko
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-12-14
  • [Presentation] Loss of CCR5 attenuates obesity-induced insulin resistance through M2 dominant shift in adipose tissue macrophage2011

    • Author(s)
      Tsuguhito Ota, Kazuki Sawamoto, Hironori Kitade, Yasuhiko Yamamoto, Hiroshi Inoue, Toshinari Takamura, Ken-ichi Miyamoto, Hiroshi Yamamoto Naofumi Mukaida, Shuichi Kaneko
    • Organizer
      第21回2011年国際糖尿病学会議(IDF2011)
    • Place of Presentation
      ドバイ(アラブ首長国連邦)
    • Year and Date
      2011-12-08
  • [Presentation] 肥満による炎症とインスリン抵抗性をリンクするCCR5の意義~脂肪組織マクロファージの量および質の調整への関与~2011

    • Author(s)
      太田嗣人,澤本一樹,北出紘規,山本靖彦,井上啓,篁俊成,山本博,向田直史,金子周一
    • Organizer
      第26回日本糖尿病合併症学会
    • Place of Presentation
      大宮ソニックシティ(埼玉県)
    • Year and Date
      2011-10-14
  • [Presentation] CCR5の欠損はob/obマウスの脂肪組織の炎症を軽減しインスリン抵抗性を改善する2011

    • Author(s)
      太田嗣人,北出紘規,澤本一樹,井上啓,金子周一
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      淡路夢舞台国際会議場(兵庫県)
    • Year and Date
      2011-09-24
  • [Presentation] CCR5 deficiency attenuates obesity-induced insulin resistance through M2 dominant shift in adipose tissue macrophage2011

    • Author(s)
      T. Ota, K. Sawamoto, H. Kitade, Y. Yamamot o, H. Inoue, T. Takamura, H. Yamamoto, N. M ukaida, S. Kaneko
    • Organizer
      第47回欧州糖尿病学会議総会
    • Place of Presentation
      日リスボン(ポルトガル)
    • Year and Date
      2011-09-15
  • [Presentation] CCR5 plays a critical role in the inflammatory adipose tissue response to high-fat feeding and obesity by regulating both macrophage recruitment and M1/M2 status2011

    • Author(s)
      TSUGUHITO OTA, KAZUKI SAWAMOTO, HIRONORI KITADE, YASUHIKO YAMAMOTO. HIROSHI INOUE, TOSHINARI TAKAMURA, KEN-ICHI MIYAMOTO, HIROSHI YAMAMOTO, NAOFUMI MUKAIDA, SHUICHI KANEKO
    • Organizer
      第71回アメリカ糖尿病学会
    • Place of Presentation
      サンディエゴ(米国)
    • Year and Date
      2011-06-24
  • [Presentation] CCR5 ablation prevents insulin resistance by high-fat feeding or leptin deficiency2011

    • Author(s)
      T Ota, H Kitade, K Sawamoto, H Inoue, T Takamura, K Miyamoto, N Mukaida, S Kaneko
    • Organizer
      日本分子生物学会第11回春季シンポジウム
    • Place of Presentation
      石川県立音楽堂(石川)
    • Year and Date
      2011-05-26
  • [Presentation] CCR5欠損はob/obマウスの脂肪組織の炎症を軽減し糖代謝異常を改善する2011

    • Author(s)
      太田嗣人,北出紘規,澤本一樹,井上啓,篁俊成,宮本謙一,向田直史,金子周一
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      ロイトン札幌(北海道)
    • Year and Date
      2011-05-21
  • [Presentation] 肥満によるる脂肪組織マクロファージの量の変化と質の調節が関わるインスリン抵抗性の発症にはCCR5によ2011

    • Author(s)
      澤本一樹,北出紘規, Ni Yinhua,山本靖彦,井上啓,篁俊成,宮本謙一,山本博,向田直史,金子周一,太田嗣人
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      ロイトン札幌(北海道)
    • Year and Date
      2011-05-21
  • [Presentation] ケモカイン受容体CCR5の欠損は脂肪組織の炎症と全身のインスリン抵抗性を改善する2011

    • Author(s)
      太田嗣人,北出紘規,澤本一樹,井上啓,篁俊成,宮本謙一,向田直史,金子周一
    • Organizer
      第84回日本内分泌学会学術総会
    • Place of Presentation
      神戸国際会議場(兵庫)
    • Year and Date
      2011-04-23
  • [Presentation] CCR5 Ablation Prevents Insulin Resistance Induced by High-Fat Feeding or Leptin Deficiency2010

    • Author(s)
      KAZUKI SAWAMOTO, TSUGUHITO OTA, HIRONORI KITADE, HIROSHI INOUE, TOSHINARI TAKAMURA, KEN-ICHI MIYAMOTO, NAOFUMI MUKAIDA, SHUICHI KANEKO
    • Organizer
      第33回日本分子生物学会年会、第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場(兵庫)
    • Year and Date
      2010-12-10
  • [Presentation] インスリン抵抗性の形成におけるケモカイン受容体CCR5の役割2010

    • Author(s)
      太田嗣人,北出紘規,澤本一樹,井上啓,篁俊成,宮本謙一,向田直史,金子周一
    • Organizer
      第22回日本分子糖尿病シンポジウム
    • Place of Presentation
      東京コンファレンスセンター品川(東京)
    • Year and Date
      2010-12-04
  • [Presentation] インスリン抵抗性形成におけるケモカインレセプターCCR5の役割2010

    • Author(s)
      北出紘規,太田嗣人,澤本一樹,井上啓,篁俊成,宮本謙一,向田直史,金子周一
    • Organizer
      第25回日本糖尿病合併症学会
    • Place of Presentation
      びわ湖ホール(滋賀)
    • Year and Date
      2010-10-22
  • [Presentation] CCR5 PROMOTES ADIPOSE TISSUE INFLAMMATION AND WHOLE-BODY INSULIN RESISTANCE2010

    • Author(s)
      T Ota, H Kitade, K Sawamoto, H Inoue, T Takamura, K Miyamoto, N Mukaida, S Kaneko
    • Organizer
      第8回国際糖尿病連合西太平洋地区会議
    • Place of Presentation
      釜山(韓国)
    • Year and Date
      2010-10-19
  • [Presentation] 肥満による炎症とインスリン抵抗性の形成によるケモカイン受容体CCR5の重要性2010

    • Author(s)
      太田嗣人,北出紘規,澤本一樹,井上啓,向田直史,金子周一
    • Organizer
      第31回日本肥満学会
    • Place of Presentation
      前橋テルサ(群馬)
    • Year and Date
      2010-10-01
  • [Presentation] CCR5 promotes adipose tissue inflammation and Insulin resistance in obesity2010

    • Author(s)
      Tsuguhito Ota, Hironori Kitade, Kazuki Sawamoto, Hiroshi Inoue, Shuichi Kaneko
    • Organizer
      第46回欧州糖尿病学会議
    • Place of Presentation
      ストックホルム(スウェーデン)
    • Year and Date
      2010-09-23
  • [Presentation] KANEKO, CCR5 Ablation Prevents Insulin Resistance Induced by High-Fat Feeding or Leptin Deficiency2010

    • Author(s)
      TSUGUHITO OTA, HIRONORI KITADE, KAZUKI SAWAMOTO, HIROSHI INOUE, TOSHINARI TAKAMURA, KEN-ICHI MIYAMOTO, NAOFUMI MUKAIDA, SHUICHI KANEKO
    • Organizer
      第70回アメリカ糖尿病学会
    • Place of Presentation
      オーランド(米国)
    • Year and Date
      2010-06-27
  • [Presentation] インスリン抵抗性の形成におけるケモカインレセプターCCR5の役割2010

    • Author(s)
      太田嗣人,北出紘規,澤本一樹,井上啓,篁俊成,宮本謙一,向田直史,金子周一
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山全日空ホテル(岡山)
    • Year and Date
      2010-05-29
  • [Remarks]

    • URL

      http://ota.w3.kanazawa-u.ac.jp/

URL: 

Published: 2013-07-31  

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