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Identification of ChREBP-mediated Acetate Metabolism

Research Project

Project/Area Number 20K11645
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionFujita Health University (2021-2022)
Gifu University (2020)

Principal Investigator

IIZUKA Katsumi  藤田医科大学, 医学部, 教授 (40431712)

Co-Investigator(Kenkyū-buntansha) 堀川 幸男  岐阜大学, 医学部附属病院, 准教授 (10323370)
矢部 大介  岐阜大学, 大学院医学系研究科, 教授 (60378643)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsChREBP / スクロース / 酢酸 / フルクトース / 脂肪酸合成 / 腸内細菌叢 / 小腸 / 肝臓 / 腸内細菌 / Acetate / Gut microbiota / Liver
Outline of Research at the Start

食物繊維摂取による肥満予防効果の機序の一つとして、食物繊維を原料として腸内細菌により産生された酢酸の役割が注目されている。申請者はグルコース活性化転写因子ChREBPの抑制による抗肥満効果を報告した。ChREBP欠失マウスの腸内細菌叢の解析結果から、ChREBP欠失マウスでは腸内細菌による酢酸産生増加が予想されるため、ChREBP抑制による抗肥満効果は酢酸を介する効果と考えられる。本研究ではChREBPによる血中酢酸調節機構、ChREBP抑制作用薬と食物繊維摂取の併用による肥満予防の有効性を検証する。本申請の成果は新規肥満予防法の臨床応用につながる。

Outline of Final Research Achievements

The intestinal microflora is considered necessary for the prevention of infections and the maintenance of healthy intestinal function. The mouse studies used in this study showed that when a person eats too much sugar and has a constitution that does not absorb sugar well, the production of acetic acid increases along with an increase in fecal matter. Although acetic acid concentrations increased when the body constitution had difficulty utilizing acetic acid, there were no previously known effects such as increased insulin or decreased appetite. Although various pharmacological effects of acetic acid have been reported, we should pay close attention to the blood concentration of acetic acid.

Academic Significance and Societal Importance of the Research Achievements

ChREBPの抑制を介して脂肪酸合成を抑えていると、酢酸濃度は上昇することが明らかになった。糖質を摂りすぎると、腸内細菌に偏りを生じ、酢酸産生が増える。酢酸には、脂肪酸の原料になること、空腹時にはエネルギー源になることが知られ、酢酸は腸内における細菌に対する抵抗力を高めるとされる。しかし、スクロースを負荷した時には血中酢酸濃度の増加とともに、体重減少、下痢などをきたすので、酢酸を利用しにくい体質の人は砂糖のとりすぎに注意が必要である。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (31 results)

All 2023 2022 2021 2020

All Journal Article (23 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 21 results,  Open Access: 21 results) Presentation (8 results) (of which Invited: 4 results)

  • [Journal Article] Recent Progress on Fructose Metabolism?Chrebp, Fructolysis, and Polyol Pathway2023

    • Author(s)
      Iizuka Katsumi
    • Journal Title

      Nutrients

      Volume: 15 Issue: 7 Pages: 1778-1778

    • DOI

      10.3390/nu15071778

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Editorial: Advances in the research of diabetic nephropathy, volume II2023

    • Author(s)
      Iizuka Katsumi、Yabe Daisuke、Abu-Farha Mohamed、Abubaker Jehad、Al-Mulla Fahd
    • Journal Title

      Frontiers in Endocrinology

      Volume: 14 Pages: 1135265-1135265

    • DOI

      10.3389/fendo.2023.1135265

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Editorial: Advances in the research of diabetic nephropathy2023

    • Author(s)
      Abu-Farha Mohamed、Iizuka Katsumi、Yabe Daisuke、Al-Mulla Fahd、Abubaker Jehad
    • Journal Title

      Frontiers in Endocrinology

      Volume: 13 Pages: 1116188-1116188

    • DOI

      10.3389/fendo.2022.1116188

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Graves' Disease with Thymic Hyperplasia: The Response of the Thyroid Function, Thyrotropin Receptor Autoantibody, and Thymic Size to Thiamazole Treatment2022

    • Author(s)
      Tsukada Daichi、Iizuka Katsumi、Takao Ken、Liu Yanyan、Kubota Sodai、Okamoto-Kubota Saki、Sakurai Teruaki、Imaizumi Toshinori、Sakai Mayu、Kato Takehiro、Mizuno Masami、Hirota Takuo、Suwa Tetsuya、Horikawa Yukio、Yamamoto Mayumi、Kubota Sumihisa、Yabe Daisuke
    • Journal Title

      Internal Medicine

      Volume: 61 Issue: 18 Pages: 2753-2757

    • DOI

      10.2169/internalmedicine.8710-21

    • NAID

      130008164547

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2022-09-15
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Is the Use of Artificial Sweeteners Beneficial for Patients with Diabetes Mellitus? The Advantages and Disadvantages of Artificial Sweeteners2022

    • Author(s)
      Iizuka Katsumi
    • Journal Title

      Nutrients

      Volume: 14 Issue: 21 Pages: 4446-4446

    • DOI

      10.3390/nu14214446

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Commentary: Comprehensive lipidome profiling of the kidney in early-stage diabetic nephropathy2022

    • Author(s)
      Iizuka Katsumi
    • Journal Title

      Frontiers in Endocrinology

      Volume: 13 Pages: 1015305-1015305

    • DOI

      10.3389/fendo.2022.1015305

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nutritional Assessment of Hospital Meals by Food-Recording Applications2022

    • Author(s)
      Iizuka Katsumi、Ishihara Takuma、Watanabe Mayuka、Ito Akemi、Sarai Masayoshi、Miyahara Ryoji、Suzuki Atsushi、Saitoh Eiichi、Sasaki Hitomi
    • Journal Title

      Nutrients

      Volume: 14 Issue: 18 Pages: 3754-3754

    • DOI

      10.3390/nu14183754

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of familial hypocalciuric hypercalcemia type 1 due to CASR p.Pro55Leu mutation2022

    • Author(s)
      Sumida Akira、Iizuka Katsumi、Kato Takehiro、Liu Yanyan、Kubota Sodai、Kubota-Okamoto Saki、Sakurai Teruaki、Imaizumi Toshinori、Takahashi Yoshihiro、Mizuno Masami、Takao Ken、Hirota Takuo、Suwa Tetsuya、Horikawa Yukio、Yamamoto Mayumi、Seino Yusuke、Suzuki Atsushi、Yabe Daisuke
    • Journal Title

      BMC Endocrine Disorders

      Volume: 22 Issue: 1 Pages: 164-164

    • DOI

      10.1186/s12902-022-01077-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucokinase-maturity onset diabetes mellitus in the young suggested by factory-calibrated glucose monitoring data: a case report2022

    • Author(s)
      Nao Nomura, Katsumi Iizuka, Eiichi Goshima, Kazuyoshi Hosomichi, Atsushi Tajima, Sodai Kubota, Yanyan Liu, Ken Takao, Takehiro Kato, Masami Mizuno, Takuo Hirota, Tetsuya Suwa, Yukio Horikawa, Daisuke Yabe
    • Journal Title

      Endocrine Journal

      Volume: 69 Issue: 4 Pages: 473-477

    • DOI

      10.1507/endocrj.EJ21-0526

    • NAID

      130008118747

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 遊離糖類・添加糖類と疾患との関連2022

    • Author(s)
      飯塚勝美
    • Journal Title

      臨床栄養

      Volume: 140 Pages: 1007-1013

    • Related Report
      2022 Annual Research Report
  • [Journal Article] 糖質摂取と生活習慣病2022

    • Author(s)
      飯塚勝美
    • Journal Title

      New Diet Therapy

      Volume: 38 Pages: 41-44

    • Related Report
      2022 Annual Research Report
  • [Journal Article] The Roles of Carbohydrate Response Element Binding Protein in the Relationship between Carbohydrate Intake and Diseases2021

    • Author(s)
      Katsumi Iizuka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22(21) Issue: 21 Pages: 12058-12058

    • DOI

      10.3390/ijms222112058

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein Amount, Quality, and Physical Activity2021

    • Author(s)
      Katsumi Iizuka
    • Journal Title

      Nutrients

      Volume: 13 Issue: 11 Pages: 3720-3720

    • DOI

      10.3390/nu13113720

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel RFX6 heterozygous mutation (p.R652X) in maturity‐onset diabetes mellitus: A case report2021

    • Author(s)
      Imaki Sakiho、Iizuka Katsumi、Horikawa Yukio、Yasuda Megumi、Kubota Sodai、Kato Takehiro、Liu Yanyan、Takao Ken、Mizuno Masami、Hirota Takuo、Suwa Tetsuya、Hosomichi Kazuyoshi、Tajima Atsushi、Fujiwara Yuuka、Yamazaki Yuji、Kuwata Hitoshi、Seino Yutaka、Yabe Daisuke
    • Journal Title

      Journal of Diabetes Investigation

      Volume: in press Issue: 10 Pages: 1914-1918

    • DOI

      10.1111/jdi.13545

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Benefit of insulin glargine/lixisenatide for reducing residual hyperglycaemia in Japan: Post hoc analysis of the LixiLan JP-O2 trial.2021

    • Author(s)
      Katsumi Iizuka, Mike Baxter, Daisuke Watanabe, Daisuke Yabe
    • Journal Title

      Diabetes, obesity & metabolism

      Volume: 23(21) Issue: 12 Pages: 2795-2803

    • DOI

      10.1111/dom.14537

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of ChREBP deficiency on adrenal lipogenesis and steroidogenesis2021

    • Author(s)
      Takao Ken、Iizuka Katsumi、Liu Yanyan、Sakurai Teruaki、Kubota Sodai、Kubota-Okamoto Saki、Imaizumi Toshinori、Takahashi Yoshihiro、Rakhat Yermek、Komori Satoko、Hirose Tokuyuki、Nonomura Kenta、Kato Takehiro、Mizuno Masami、Suwa Tetsuya、Horikawa Yukio、Sone Masakatsu、Yabe Daisuke
    • Journal Title

      Journal of Endocrinology

      Volume: 248 Issue: 3 Pages: 317-324

    • DOI

      10.1530/joe-20-0442

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report2021

    • Author(s)
      Takao Ken、Tani Ayaka、Suwa Tetsuya、Kuwabara-Ohmura Yayoi、Nonomura Kenta、Liu Yanyan、Kato Takehiro、Mizuno Masami、Hirota Takuo、Enya Mayumi、Iizuka Katsumi、Horikawa Yukio、Saigo Chiemi、Kito Yusuke、Miyazaki Tatsuhiko、Ohe Naoyuki、Iwama Toru、Yabe Daisuke
    • Journal Title

      BMC Endocrine Disorders

      Volume: 21 Issue: 1 Pages: 13-13

    • DOI

      10.1186/s12902-020-00675-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue2020

    • Author(s)
      Iizuka Katsumi、Takao Ken、Yabe Daisuke
    • Journal Title

      Frontiers in Endocrinology

      Volume: 11 Pages: 587189-587189

    • DOI

      10.3389/fendo.2020.587189

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Review of Recent Findings on Meal Sequence: An Attractive Dietary Approach to Prevention and Management of Type 2 Diabetes2020

    • Author(s)
      Kubota Sodai、Liu Yanyan、Iizuka Katsumi、Kuwata Hitoshi、Seino Yutaka、Yabe Daisuke
    • Journal Title

      Nutrients

      Volume: 12 Issue: 9 Pages: 2502-2502

    • DOI

      10.3390/nu12092502

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Metagenomics in Precision Nutrition2020

    • Author(s)
      Iizuka Katsumi、Yabe Daisuke
    • Journal Title

      Nutrients

      Volume: 12 Issue: 6 Pages: 1668-1668

    • DOI

      10.3390/nu12061668

    • Related Report
      2020 Research-status 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 <i>HNF1B</i> gene2020

    • Author(s)
      Kuwabara-Ohmura Yayoi、Iizuka Katsumi、Liu Yanyan、Takao Ken、Nonomura Kenta、Kato Takehiro、Mizuno Masami、Hosomichi Kazuyoshi、Tajima Atsushi、Miyazaki Tatsuhiko、Horikawa Yukio、Yabe Daisuke
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 9 Pages: 981-988

    • DOI

      10.1507/endocrj.EJ20-0038

    • NAID

      130007910088

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardioprotective effects of GLP‐1(28‐36a): A degraded metabolite or GLP‐1’s better half?2020

    • Author(s)
      Liu Y, Kubota S, Iizuka K, Yabe D
    • Journal Title

      Journal of Diabetes Investigation

      Volume: . Issue: 6 Pages: 1422-1425

    • DOI

      10.1111/jdi.13302

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 小腸ChREBPはフルクトースの吸収だけでなく、腸内細菌を介した酢酸産生も調節する2023

    • Author(s)
      飯塚勝美 土田宏美 鷹尾賢 劉彦言 窪田創大 窪田紗希 今泉俊則 加藤丈博 鈴木渓 富田弘之 堀川幸男 矢部大介
    • Organizer
      第66回 日本糖尿病学会年次学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] インスリン抵抗性状態ではChREBP活性は減弱する2023

    • Author(s)
      後田ちひろ、亀井優香、今度匡祐、土田宏美、清野祐介、 長尾静子、矢部大介、鈴木敦詞、飯塚勝美
    • Organizer
      第66回 日本糖尿病学会年次学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] グルコース活性化転写因子ChREBPに注目した小腸ー腸内細菌ー肝を軸としたフルクトース 代謝メカニズム2022

    • Author(s)
      飯塚勝美
    • Organizer
      第95回日本生化学会大会 シンポジウム スクロース フルクトース代謝の新パラダイム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 脂肪性肝疾患の成因と栄養管理の理論2021

    • Author(s)
      飯塚勝美
    • Organizer
      第24・25回日本病態栄養学会年次学術集会 シンポジウム17 肝疾患の栄養管理(脂肪性肝疾患・肝硬変)
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 糖質摂取と生活習慣病2021

    • Author(s)
      飯塚勝美
    • Organizer
      第42回日本臨床栄養協会総会 サプリメントフォーラム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 1818-P: High-Sucrose Diet Causes Increased Hepatic Histone Acetylation Due to Increased Bacterial Acetate Production and Reduced Lipogenesis in ChREPB-Deficient Mice2020

    • Author(s)
      Katsumi Iizuka, Ken Takao, Yanyan Liu, Kenta Nonomura, Takehiro Kato, Masami Mizuno, Yuka Fujiwara, Hitoshi Kuwata, Yutaka Seino, Yukio Horikawa, Daisuke Yabe
    • Organizer
      80TH virtual SCIENTIFIC SESSIONS, The American Diabetes Association's annual Scientific Sessions
    • Related Report
      2020 Research-status Report
  • [Presentation] グルコース活性化転写因子ChREBPと栄養/疾患の関わりについて2020

    • Author(s)
      飯塚勝美
    • Organizer
      第77回日本栄養・食糧学会中部支部大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] インスリングラルギン/リキシセナチド配合剤による残余高血糖改善効果の検討:LixiLan JP-L試験 Post-hoc解析2020

    • Author(s)
      飯塚勝美、矢部大介、Mike Baxter、渡邊 大丞、金藤 秀明
    • Organizer
      第63回 日本糖尿病学会年次学術集会,
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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