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Elucidation of the mechanisms underlying n-3 polyunsaturated fatty acids mediated degradation of ChREBP

Research Project

Project/Area Number 26750041
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Eating habits
Research InstitutionKobe University

Principal Investigator

NAKAGAWA TSUTOMU  神戸大学, 医学(系)研究科(研究院), 講師 (50722063)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsChREBP / n-3系脂肪酸 / SUMO
Outline of Final Research Achievements

n-3 polyunsaturated fatty acids (PUFA) can reduce plasma triglyceride (TG) level. However, the underlying mechanism of plasma TG reduction remains unclear. Carbohydrate response element-binding protein (ChREBP) is a transcription factor responsible for the coordinated metabolism of carbohydrate and fat synthesis. It was reported that the inhibition of ChREBP in leptin-deficient mice improved plasma TG level. Therefore, it was suggested that ChREBP could be a protein affected by n-3 PUFA, which was involved in reducing plasma TG level. In this study, it was shown that n-3 PUFA could promote the degradation of ChREBP. Moreover, it was found that ChREBP was degraded via the autophagy-lysosomal pathway. The inhibitory effect on ChREBP activity by n-3 PUFA disappeared when the degradation of ChREBP was inhibited by chloroquine treatment. These results suggested that n-3 PUFA promoted the degradation of ChREBP by inducing autophagy, resulting in reduction of plasma TG level.

Report

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

    (14 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (4 results) Remarks (3 results)

  • [Int'l Joint Research] UT Southwestern Medical Center(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Metabolite Regulation of Nuclear Localization of Carbohydrate Response Element-binding Protein (ChREBP). Role of AMP as an Allosteric Inhibitor.2016

    • Author(s)
      Sato S., Jung H., Nakagawa T., Pawlosky R., Takeshima T., Lee W. R., Sakiyama H., Laxman S., Wynn R. M., Tu B., MacMillan J. B., De Brabander J. K., Veech R. L., Uyeda K.
    • Journal Title

      Journal of Biological Chemistry

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population.2016

    • Author(s)
      Yamamoto K., Ioroi T., Kanaya K., Shinomiya K., Komoto S., Hirata S., Harada K., Watanabe A., Suno M., Nishioka T., Kume M., Makimoto H., Nakagawa T., Hirano T., Miyake H., Fujisawa M., Hirtai M.
    • Journal Title

      Medical Oncology

      Volume: 33 Issue: 3 Pages: 24-24

    • DOI

      10.1007/s12032-016-0733-0

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors: A Retrospective Analysis in Japanese Patients.2016

    • Author(s)
      Yamamoto K., Shinomiya K., Ioroi T., Hirata S., Harada K., Suno M., Nishioka T., Kume M., Makimoto H., Nakagawa T., Hirano T., Bito T., Nishigori C., Miyake H., Fujisawa M., Hirai M.
    • Journal Title

      Targeted Oncology

      Volume: 11 Issue: 1 Pages: 93-99

    • DOI

      10.1007/s11523-015-0382-9

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of epithelial-mesenchymal transition via activation of epidermal growth factor receptor contributes to sunitinib resistance in human renal cell carcinoma cell lines.2015

    • Author(s)
      Mizumoto A., Yamamoto K., Nakayama Y., Takara K., Nakagawa T., Hirano T., Hirai M.
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics

      Volume: 355 Issue: 2 Pages: 152-158

    • DOI

      10.1124/jpet.115.226639

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apoptotic Effects of the Extracts of Cordyceps militaris via Erk Phosphorylation in a Renal Cell Carcinoma Cell Line.2015

    • Author(s)
      Yamamoto K., Shichiri H., Uda A., Yamashita K., Nishioka T., Kume M., Makimoto H., Nakagawa T., Hirano T., Hirai M.
    • Journal Title

      Phytotherapy Research

      Volume: 25 Issue: 5 Pages: 707-713

    • DOI

      10.1002/ptr.5305

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of toxicity of sorafenib and sunitinib for human keratinocytes with inhibition of signal transduction and activator of transcription 3 (STAT3).2014

    • Author(s)
      2.Yamamoto K., Mizumoto A., Nishimura K., Uda A., Mukai A., Yamashita K., Kume M., Makimoto H., Bito T., Nishigori C., Nakagawa T., Hirano T., Hirai M.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 7 Pages: e102110-e102110

    • DOI

      10.1371/journal.pone.0102110

    • NAID

      120005465541

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Carbohydrate response element-binding protein (ChREBP)の活性制御に及ぼす核移行/核外搬出 シグナルの影響2015

    • Author(s)
      中川 勉、吉村 友希、崎山 晴彦、山本 和宏、藤原 範子、 鈴木 敬一郎、平井 みどり
    • Organizer
      BMB2015
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] ChREBP-βの活性化機構の解明2015

    • Author(s)
      吉村友希、中川勉、崎山晴彦、山本和宏、江口裕伸、藤原範子、平野剛、鈴木 敬一郎、平井みどり
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(兵庫県・神戸市)
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規mTORC1結合因子P110の栄養感知システムとしての生理機能解析2014

    • Author(s)
      七里博章、山本和宏、中川 勉、平野 剛、平井 みどり
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ChREBPと14-3-3の結合に影響を与える代謝物の同定2014

    • Author(s)
      中川勉、吉村友希、Qiang Ge、Robert pawlosky、R. Max Wynn、山本和宏、平 野剛、Richard L. Veech、Kosaku Uyeda、平井みどり
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府・京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Remarks] 神戸大学大学院医学研究科 薬物動態学・薬剤学分野

    • URL

      http://www.med.kobe-u.ac.jp/yakudo/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 神戸大学大学院医学研究科 薬物動態学・薬剤学分野ホームページ

    • URL

      http://www.med.kobe-u.ac.jp/yakudo

    • Related Report
      2014 Research-status Report
  • [Remarks] 神戸大学病院薬剤部ホームページ

    • URL

      http://www.hosp.kobe-u.ac.jp/yakuzai/Pharm/kobepharm.html

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2022-01-27  

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