• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Effect of obesity and diabetes on liver cancer and tumor-associated macrophage polarization

Research Project

Project/Area Number 25461333
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionUniversity of Toyama

Principal Investigator

USUI Isao  富山大学, 大学病院, 講師 (50377272)

Co-Investigator(Kenkyū-buntansha) HAYAKAWA Yoshihiro  富山大学, 和漢医薬学総合研究所, 准教授 (10541956)
Co-Investigator(Renkei-kenkyūsha) TSUNEYAMA Koichi  徳島大学, 大学院医歯薬学研究部(医学系), 教授 (10293341)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords肝がん / 肥満 / 糖尿病 / マクロファージ / HIF-1a / 低酸素 / HIF-1 / 肝細胞がん / 腫瘍関連マクロファージ
Outline of Final Research Achievements

In this study, the effect of high fat diet (HFD)-induced obesity and/or diabetes mellitus on liver cancer and tumor-associated macrophages (TAMs) was examined. Model mice for liver cancer were generated by intraperitoneally injecting dimethylnitrosamine (DEN), a chemical carcinogen. HFD treatment increased the number and the size of DEN-induced liver cancers, as well as the number of macrophages inside or outside of the cancers.
In macrophage-specific HIF-1a knockout mice (KO), the expression levels of both M1 and M2 activation markers were decreased in macrophages separated from the liver. Interestingly, the number of liver cancers was decreased in the KO mice, although their size was not affected, comparedwithe the wild type mice. These results suggest that TAMs, which were activated in HIF-1a-dependent manor, may promote carcinogenesis in the liver of HFD-fed mice.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (27 results)

All 2016 2015 2014 2013

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results) Book (5 results)

  • [Journal Article] Deletion of SIRT1 in myeloid cells impairs glucose metabolism with enhancing inflammatory response to adipose tissue hypoxia2016

    • Author(s)
      Akiko Takikawa, Isao Usui , Shiho Fujisaka, Masashi Ikutani, Satoko Senda, Shinpei Hattori, Koichi Tsuneyama, Yukiko Koshimizu, Ran Inoue, Ayumi Tanaka-Hayashi, Takashi Nakagawa, Yoshinori Nagai, Kiyoshi Takatsu, Toshiyasu Sasaoka, Hisashi Mori, Kazuyuki Tobe
    • Journal Title

      Diabetology International

      Volume: 7 Issue: 1 Pages: 59-68

    • DOI

      10.1007/s13340-015-0213-3

    • NAID

      40020774323

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adipose Tissue Hypoxia Induces Inflammatory M1 Polarity of Macrophages in HIF-1a-Dependent and HIF-1a-Independent Manners in Obese Mice.2013

    • Author(s)
      Fujisaka S, Usui I, Ikutani M, Aminuddin A, Takikawa A, Tsuneyama K, Mahmood A, Goda N, Nagai Y, Takatsu K, Tobe K..
    • Journal Title

      Diabetologia

      Volume: 56(6) Issue: 6 Pages: 1403-1412

    • DOI

      10.1007/s00125-013-2885-1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of divergent effects of astaxanthin on insulin signaling in L6 cells2013

    • Author(s)
      Ishiki M, Nishida Y, Ishibashi H, Wada T, Fujisaka S, Takikawa A, Urakaze M, Sasaoka T, Usui I, Tobe K.
    • Journal Title

      Endocrinology

      Volume: 154(8) Issue: 8 Pages: 2600-2612

    • DOI

      10.1210/en.2012-2198

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] PACAP Attenuates NMDA-Induced Retinal Damage in Association with Modulation of the Microglia/Macrophage Status into an Acquired Deactivation Subtype.2013

    • Author(s)
      Wada Y, Nakamachi T, Endo K, Seki T, Ohtaki H, Tsuchikawa D, Hori M, Tsuchida M, Yoshikawa A, Matkovits A, Kagami N, Imai N, Fujisaka S, Usui I, Tobe K, Koide R, Takahashi H, Shioda S
    • Journal Title

      J Mol Neurosci.

      Volume: 51(2) Issue: 2 Pages: 493-502

    • DOI

      10.1007/s12031-013-0017-5

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin-induced mouse model of asthma.2013

    • Author(s)
      Ichikawa T, Hayashi R, Suzuki K, Imanishi S, Kambara K, Okazawa S, Inomata M, Yamada T, Yamazaki Y, Koshimizu Y, Miwa T, Matsui S, Usui I, Urakaze M, Matsuya Y, Sasahara M, Tobe K.
    • Journal Title

      Respirology

      Volume: 18 Issue: 2 Pages: 332-339

    • DOI

      10.1111/j.1440-1843.2012.02284.x

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 肥満における脂肪組織マクロファージの機能2015

    • Author(s)
      薄井勲,瀧川章子, 戸辺一之
    • Organizer
      第36回日本肥満学会総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Myeloid Cell-specific HIF-1 alpha Deletion Protected against Insulin Resistance with Increased Angiogenesis in High Fat-fed Mice2015

    • Author(s)
      Takikawa A, Mahmood A, Nawaz A, Kado T, Senda S, Okabe K, Usui I, Tobe K.
    • Organizer
      the American Diabetes Association's 75th Scientific Sessions
    • Place of Presentation
      米国 ボストン市
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マクロファージSIRT1による糖代謝制御2015

    • Author(s)
      薄井勲,瀧川章子, 戸辺一之
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関市
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] マクロファージ特異的HIF-1α欠損による食餌性肥満マウスの糖代謝・脂肪組織への影響2015

    • Author(s)
      4.瀧川章子,Arshad Mahmood,Allah Nawaz,角朝信,山本誠士,常山幸一,岡部圭介,仙田聡子,中川崇,薄井勲,合田亘人,戸辺一之
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関市
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] マクロファージ特異的HIF-1α欠損は高脂肪食負荷マウスの糖代謝を改善する2015

    • Author(s)
      3.瀧川章子,Arshad Mahmood,Allah Nawaz,角朝信,仙田聡子,薄井勲,合田亘人,戸辺一之
    • Organizer
      第88回日本内分泌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] マクロファージ特異的HIF-1α欠損は高脂肪食負荷マウスの糖代謝を改善する2014

    • Author(s)
      瀧川章子,Mahmood A,薄井勲,戸邉一之
    • Organizer
      日本内分泌学会第32回内分泌代謝学サマーセミナー
    • Place of Presentation
      山梨
    • Year and Date
      2014-07-10 – 2014-07-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Myeloid Cell-Specific Deletion of Hypoxia-Inducible Factor 1-alpha Gene Protected against Diet-Induced Insulin Resistance in Mice.2014

    • Author(s)
      Takikawa A, Mahmood A, Fujisaka S, Nakagawa T, Senda S, Aminuddin A, Usui I, Tobe K.
    • Organizer
      74th scientific sessions of American Diabetes Association
    • Place of Presentation
      San Francisco
    • Year and Date
      2014-06-13 – 2014-06-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 肥満脂肪組織の慢性炎症と低酸素シグナル2014

    • Author(s)
      薄井 勲、瀧川章子、戸辺一之
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 脂肪組織の慢性炎症における低酸素とマクロファージの関連2014

    • Author(s)
      瀧川章子,薄井勲,藤坂志帆,Mahmood A,仙田聡子,Aminuddin,岡部圭介,角朝信,小清水由紀子,戸辺一之
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Depletion of CD206-positive cells is associated with increased white adipose tissue proliferation.2014

    • Author(s)
      Aminuddin, Takikawa A, Usui I, Fujisaka S, Mahmood A, Nawaz A, Tobe K
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Myeloid-Specific deletion of Hypoxia-inducible factor 1-alpha gene protected against Diet induced Insulin resistance.2014

    • Author(s)
      9.Mahmood A, Senda S, Nakagawa T, Fujisaka S, Takikawa A, Aminuddin A, Nawaz A, Usui I, Tobe K
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] マクロファージ特異的HIF-1α欠損は高脂肪食負荷マウスの糖代謝を改善する2014

    • Author(s)
      瀧川章子,Mahmood A,藤坂志帆,仙田聡子,Aminuddin,中川崇,薄井勲,戸邉一之
    • Organizer
      第51回日本臨床分子医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-04-11 – 2014-04-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 脂肪組織低酸素とインスリン抵抗性2013

    • Author(s)
      薄井勲、藤坂志帆, 瀧川章子、Arshad Mahmood、戸辺一之
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Myeloid cell-specific deletion of SIRT1 enhanced inflammatory response to hypoxia with glucose intolerance2013

    • Author(s)
      Akiko Takikawa, Isao Usui, Satoko Senda, Shiho Fujisaka, Yukiko Koshimizu, Koichi Tsuneyama, Amiuddin, Arshad Mahmood, Masashi Ikutani, Yoshinori Nagai, Kiyoshi Takatsu, Hisashi Mori, Kazuyuki Tobe
    • Organizer
      The American Diabetes Association's 73rd Scientific Sessions
    • Place of Presentation
      Chicago
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Adipose Tissue Hypoxia Induces Inflammatory M1 Polarity of Macrophages in HIF-1a -Dependent and HIF-1a Independent Manners in Obese Mice.2013

    • Author(s)
      Fujisaka S, Usui I, Ikutani M, Aminuddin A, Takikawa A, Tsuneyama K, Mahmood A, Goda N, Nagai Y, Takatsu K, and Tobe K
    • Organizer
      The American Diabetes Association's 73rd Scientific Sessions
    • Place of Presentation
      Chicago
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Depletion of Cd206-positive cells is associated with increased WAT proliferation and improved insulin sensitivity.2013

    • Author(s)
      Aminuddin, Shiho Fujisaka, Hisashi Mori, Kenji Kohno, Isao Usui, Kazuyuki Tobe.
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 骨髄球特異的なHif-1α遺伝子の欠損は糖代謝を改善する2013

    • Author(s)
      マハムド アルシャド, 薄井勲, 仙田聡子, 藤坂志帆, 瀧川章子, Aminuddin, 中川崇, 戸邉一之
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 医学のあゆみ2016

    • Author(s)
      薄井 勲,戸邉一之
    • Total Pages
      4
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2015 Annual Research Report
  • [Book] 月刊糖尿病2015

    • Author(s)
      瀧川章子,薄井 勲,戸邉一之
    • Total Pages
      8
    • Publisher
      医学出版
    • Related Report
      2015 Annual Research Report
  • [Book] Annual Review糖尿病・内分泌20142014

    • Author(s)
      薄井 勲、戸辺一之
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2014 Research-status Report
  • [Book] 血管医学2014

    • Author(s)
      薄井 勲、戸辺一之
    • Total Pages
      8
    • Publisher
      メディカルレビュー社
    • Related Report
      2014 Research-status Report
  • [Book] 医学のあゆみ2014

    • Author(s)
      薄井 勲、戸辺一之
    • Total Pages
      4
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi