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

Identification of a new mechanism for ketogenesis by ChREBP

Research Project

Project/Area Number 17K00850
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Eating habits
Research InstitutionGifu University

Principal Investigator

Iizuka Katsumi  岐阜大学, 医学部附属病院, 講師 (40431712)

Co-Investigator(Kenkyū-buntansha) 武田 純  岐阜大学, 大学院医学系研究科, 非常勤講師 (40270855)
堀川 幸男  岐阜大学, 医学部附属病院, 准教授 (10323370)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsChREBP / ケトン食 / FGF21 / Angptl8 / Angptl3 / 3-OH-butyric acid / PPARα / PPAR alpha / hepatocyte / liver / Ketogenesis / Fgf21 / ketone body / Fgf-21 / β-hydroxybutyrate / de novo lipoenesis / 脂質異常症 / 肥満 / ケトン代謝 / インスリン / グルカゴン
Outline of Final Research Achievements

The glucose-activated transcription factor ChREBP is a transcription factor that is activated by glucose and fructose and mediates de novo lipogenesis. This study elucidated the molecular mechanism of the reduction of ketone synthesis by activation or inhibition of ChREBP. Ketones are a source of energy during fasting, and ketogenic diets are useful as an anti-obesity diet, but they are also life-threatening substances when accumulated in high concentrations. This study is an important finding for the safe use of ketogenic diets.

Academic Significance and Societal Importance of the Research Achievements

糖質を脂質に変えるセンサータンパクであるChREBPは機能が亢進しても逆に低下しても、血液中の脂質であるトリグリセリドやケトンの濃度を低下させることが明らかとなった。両者は長い目で見るとともに空腹時に使われるエネルギーとなるため、ChREBPが摂食時に活性化され、間接的に空腹時のエネルギー調節に関与することを示唆する。またケトン食のような低炭水化物食は脂肪肝につながることが明らかとなった。したがって、間食などをせずに、適量の炭水化物を含む食事を規則正しい時間に摂取することが、血中の糖質脂質濃度調節に重要であると考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (27 results)

All 2020 2019 2018

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (3 results)

  • [Journal Article] SGLT2 Inhibitor and GLP-1 Receptor Agonist Combination Therapy Substantially Improved the Renal Function in a Patient with Type 2 Diabetes: Implications for Additive Renoprotective Effects of the Two Drug Classes2020

    • Author(s)
      Nonomura Kenta、Iizuka Katsumi、Kuwabara-Ohmura Yayoi、Yabe Daisuke
    • Journal Title

      Internal Medicine

      Volume: 59 Issue: 12 Pages: 1535-1539

    • DOI

      10.2169/internalmedicine.4323-19

    • NAID

      130007854991

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2020-06-15
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the HNF1B gene.2020

    • Author(s)
      Kuwabara-Ohmura Y , Iizuka K , Liu Y , Takao K , Nonomura K , Kato T , Mizuno M , Hosomichi K , Tajima A , Miyazaki T , Horikawa Y , Yabe D
    • Journal Title

      Endocrine Journal

      Volume: in press

    • NAID

      130007910088

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Type 1 Diabetes Mellitus and Klinefelter Syndrome2019

    • Author(s)
      Sakurai Teruaki、Iizuka Katsumi、Kato Takehiro、Takeda Jun
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 2 Pages: 259-262

    • DOI

      10.2169/internalmedicine.1051-18

    • NAID

      130007579731

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-01-15
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sodium glucose cotransporter2 inhibitor and sarcopenia in a lean elderly adult with type 2 diabetes: A case report2019

    • Author(s)
      Yasuda Megumi、Iizuka Katsumi、Kato Takehiro、Liu Yanyan、Takao Ken、Nonomura Kenta、Mizuno Masami、Yabe Daisuke
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 11 Issue: 3 Pages: 745-747

    • DOI

      10.1111/jdi.13137

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A rare case of autoimmune polyglandular syndrome with Sjogren’s syndrome and primary hypoparathyroidism2019

    • Author(s)
      Iizuka Katsumi、Mizuno Masami、Nonomura Kenta、Yabe Daisuke
    • Journal Title

      BMJ Case Reports

      Volume: 12 Issue: 5 Pages: e228634-e228634

    • DOI

      10.1136/bcr-2018-228634

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High Dose Prednisolone Lowers Plasma Glycated Albumin Levels Compared to Actual Glycemic Control: A Retrospective Observational Study2019

    • Author(s)
      Mizuno Masami、Iizuka Katsumi、Ishihara Takuma、Fukaya Shusaku、Yoshida Shunji、Takeda Jun
    • Journal Title

      Diabetes Therapy

      Volume: 10 Issue: 1 Pages: 269-276

    • DOI

      10.1007/s13300-018-0552-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ChREBP Reciprocally Regulates Liver and Plasma Triacylglycerol Levels in Different Manners2018

    • Author(s)
      Iizuka Katsumi、Takao Ken、Kato Takehiro、Horikawa Yukio、Takeda Jun
    • Journal Title

      Nutrients

      Volume: 10 Issue: 11 Pages: 1699-1699

    • DOI

      10.3390/nu10111699

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calpain-10 regulates actin dynamics by proteolysis of microtubule-associated protein 1B2018

    • Author(s)
      Hatta Tomohisa、Iemura Shun-ichiro、Ohishi Tomokazu、Nakayama Hiroshi、Seimiya Hiroyuki、Yasuda Takao、Iizuka Katsumi、Fukuda Mitsunori、Takeda Jun、Natsume Tohru、Horikawa Yukio
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 16756-16756

    • DOI

      10.1038/s41598-018-35204-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ChREBP-Knockout Mice Show Sucrose Intolerance and Fructose Malabsorption2018

    • Author(s)
      Kato Takehiro、Iizuka Katsumi、Takao Ken、Horikawa Yukio、Kitamura Tadahiro、Takeda Jun
    • Journal Title

      Nutrients

      Volume: 10 Issue: 3 Pages: 340-340

    • DOI

      10.3390/nu10030340

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ChREBP Rather Than SHP Regulates Hepatic VLDL Secretion2018

    • Author(s)
      Niwa Hiroyuki、Iizuka Katsumi、Kato Takehiro、Wu Wudelehu、Tsuchida Hiromi、Takao Ken、Horikawa Yukio、Takeda Jun
    • Journal Title

      Nutrients

      Volume: 10 Issue: 3 Pages: 321-321

    • DOI

      10.3390/nu10030321

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ChREBPとPPARαによるFGF21の転写調節制御の分子機序に関する検討:ChREBP欠損マウスにおけるPPARα活性化薬ぺマフィブラートの効果2020

    • Author(s)
      鷹尾賢、飯塚勝美、劉彦言、野々村健太、加藤丈博、水野正巳、堀川幸男、矢部大介
    • Organizer
      第63回日本糖尿病学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The importance of islet, hepatic, and intestinal ChREBP in metabolic diseases2019

    • Author(s)
      Katsumi Iizuka, Daisuke Yabe
    • Organizer
      Asia islet biology and incretin symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ChREBPを介したスクロース/フルクトース代謝機構2019

    • Author(s)
      飯塚 勝美、矢部 大介
    • Organizer
      第73回 日本栄養食糧学会 シンポジウム 砂糖の最新栄養科学 -分子栄養学から日本食-
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] The Importance of Intestinal ChREBP in the Regulation of Sucrose and Fructose Metabolism2019

    • Author(s)
      Katsumi Iizuka, Daisuke Yabe
    • Organizer
      第62回 日本糖尿病学会年次学術集会  シンポジウム「Gut links nutrition, metabolism and diabetes (腸管がつなぐ栄養・代謝・糖尿病)」
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ChREBPの肝および血中トリグリセリドに対する調節機序の違い―Fgf21およびAngptl3に注目した解析―2019

    • Author(s)
      飯塚勝美、鷹尾賢、加藤丈博、堀川幸男、武田純、矢部大介
    • Organizer
      第6回 肝臓と糖尿病・代謝研究会 研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小腸スクロース/フルクトース代謝におけるChREBPの 役割2019

    • Author(s)
      加藤丈博、飯塚勝美、堀川幸男、武田純、矢部大介
    • Organizer
      第56回 日本臨床分子医学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 高ケトン食の有効性 安全性に関する検討2019

    • Author(s)
      鷹尾 賢、飯塚勝美、堀川幸男、武田純、矢部大介
    • Organizer
      第56回 日本臨床分子医学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ChREBP欠失マウスではSGLT2阻害薬による血糖低下作用が減弱する2019

    • Author(s)
      加藤丈博、飯塚勝美、鷹尾 賢、堀川幸男、矢部大介
    • Organizer
      第92回 日本内分泌学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] FGF-21誘導におけるChREBPとPPARαの協調作用-ペマフィブラートを用いた検討-2019

    • Author(s)
      鷹尾賢、飯塚勝美、加藤丈博、堀川幸男、矢部大介
    • Organizer
      第92回 日本内分泌学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腸内細菌叢変化に注目した ChREBP 遺伝子欠失マウスのスクロース不耐症発症機構の検討2018

    • Author(s)
      飯塚 勝美、加藤 丈博、鷹尾 賢、堀川 幸男、北村 忠弘、武田 純
    • Organizer
      第5回 肝臓と糖尿病・代謝研究会 研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] ChREBPノックアウトマウスはスクロース不耐症のモデルマウスである2018

    • Author(s)
      加藤 丈博,飯塚 勝美,鷹尾 賢 ,土田 宏美,堀川 幸男,北村 忠弘,武田 純
    • Organizer
      第91回 日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] ChREBPがケトン体代謝に及ぼす役割2018

    • Author(s)
      鷹尾 賢、飯塚 勝美、加藤 丈博、土田 宏美、堀川 幸男、武田 純
    • Organizer
      第91回 日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] ミグリトール添加スクロース食負荷ChREBPノックアウトマウスは新たなフルクトース不耐症のモデルである2018

    • Author(s)
      加藤 丈博,飯塚 勝美,鷹尾 賢 ,土田 宏美,堀川 幸男,北村 忠弘,武田 純
    • Organizer
      第61回 日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 高ケトン食の安全性・有効性とChREBPが及ぼす影響2018

    • Author(s)
      鷹尾 賢、飯塚 勝美、加藤 丈博、土田 宏美、堀川 幸男、武田 純
    • Organizer
      第61回 日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Book] The Role of Carbohydrate Response Element-Binding Protein in the Development of Liver Diseases In Dietary Interventions in Liver Disease: Foods, Nutrients, and Dietary Supplements2019

    • Author(s)
      Katsumi Iizuka
    • Publisher
      Elsevier
    • ISBN
      9780128144671
    • Related Report
      2019 Annual Research Report
  • [Book] ChREBP and cancer In Molecular Nutrition: Carbohydrate2019

    • Author(s)
      Katsumi Iizuka
    • Publisher
      Elsevier
    • ISBN
      9780128498866
    • Related Report
      2019 Annual Research Report
  • [Book] Dietary Interventions in Liver Disease 1st Edition2019

    • Author(s)
      Katsumi Iizuka, Editors: Ronald Watson Victor Preedy
    • Total Pages
      428
    • Publisher
      Elsevier
    • ISBN
      9780128144664
    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi