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Mechanism of suppression and induction of obesity by dietary fat

Research Project

Project/Area Number 19H02909
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionOsaka Metropolitan University (2022)
Osaka Prefecture University (2020-2021)
Kyoto University (2019)

Principal Investigator

Matsumura Shigenobu  大阪公立大学, 大学院生活科学研究科, 准教授 (70467413)

Co-Investigator(Kenkyū-buntansha) 佐々木 勉  大阪大学, 大学院医学系研究科, 寄附講座准教授 (20534879)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2021: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords油脂 / 嗜好 / 肥満 / 糖尿病 / 転写因子 / 脂肪 / 神経細胞 / 嗜好性 / 油脂摂取
Outline of Research at the Start

油脂の過剰摂取は肥満を招き様々な生活習慣病を誘発し、現代社会の大きな問題となっている。これまでの研究により油脂の‘嗜好性’は過食を招くと同時に自律神経を活性化することにより全身のエネルギー代謝を亢進させることが明らかとなっている。詳細な機構は不明であるが、このエネルギー消費の亢進が急激な体重増加を抑制していると考えられる。一方で、食欲とエネルギー消費のバランスを崩壊させ肥満を誘導する因子として、ストレスが挙げられるが、ストレスが油脂の嗜好性とエネルギー代謝に与える影響は不明である。そこで本研究では、油脂の嗜好性とエネルギー代謝およびストレスとの間にある相互作用の解明を行う。

Outline of Final Research Achievements

We tried to clarify the mechanism that suppresses obesity or promotes obesity by dietary fat ingestion. We found that dietary fat ingestion suppresses obesity by accelerating fatty acid oxidation in brown adipose tissue and liver. In contrast, dietary fat ingestion did not affect skeletal muscle fat metabolism. Next, we examined the role of transcription factor CREB on the addictive behavior for dietary fat. We found that the inhibition of CREB activity only in MC4R neurons caused the increase in fat ingestion and the decrease in energy consumption. Consequently, the mice became obesity. These results suggest that CREB activity in MC4R neurons plays an important role on the regulation of fat ingestion, appetite and energy metabolism.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により油脂摂取にともない代謝が変化する臓器として肝臓と脂肪組織が明らかとなった。これらの臓器の代謝が肥満予防に重要であるとともに、これらの臓器の代謝不全が肥満の一因となることが予想される。このため、肝臓および脂肪組織の代謝を健全に保つことが健康の維持に重要であると考えられる。また、脳内の一部の神経細胞が油脂欲求を制御していることが明らかとなった。この神経群が油脂摂取による過食の原因であるとともに過食治療の鍵となることが期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (11 results)

All 2022 2021 2019 Other

All Int'l Joint Research (5 results) Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (1 results) (of which Invited: 1 results)

  • [Int'l Joint Research] University of Texas(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Southern Denmark(デンマーク)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Salk Institute(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Kim Ravnskjaer/University of Southern Denmark(デンマーク)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Marc Montminy/Salk Institute(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Stimulation of G<sub>s</sub> signaling in MC4R cells by DREADD increases energy expenditure, suppresses food intake, and increases locomotor activity in mice2022

    • Author(s)
      Matsumura Shigenobu、Miyakita Motoki、Miyamori Haruka、Kyo Satomi、Shima Daisuke、Yokokawa Takumi、Ishikawa Fuka、Sasaki Tsutomu、Jinno Tomoki、Tanaka Jin、Goto Tsuyoshi、Momma Keiko、Ishihara Kengo、Berdeaux Rebecca、Inoue Kazuo
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 322 Issue: 5 Pages: E436-E445

    • DOI

      10.1152/ajpendo.00439.2021

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] <scp>CRTC1</scp> deficiency, specifically in melanocortin‐4 receptor‐expressing cells, induces hyperphagia, obesity, and insulin resistance2022

    • Author(s)
      Matsumura Shigenobu、Miyakita Motoki、Miyamori Haruka、Kyo Satomi、Ishikawa Fuka、Sasaki Tsutomu、Jinno Tomoki、Tanaka Jin、Fujita Kotomi、Yokokawa Takumi、Goto Tsuyoshi、Momma Keiko、Takenaka Shigeo、Inoue Kazuo
    • Journal Title

      The FASEB Journal

      Volume: 36 Issue: 12

    • DOI

      10.1096/fj.202200617r

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of CRTC1 and CRTC2 in Sim1 cells strongly increases high-fat diet intake in female mice but has a modest impact on male mice2022

    • Author(s)
      Tanaka Jin、Ishikawa Fuka、Jinno Tomoki、Miyakita Motoki、Miyamori Haruka、Sasaki Tsutomu、Yokokawa Takumi、Goto Tsuyoshi、Inoue Kazuo、Matsumura Shigenobu
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 1 Pages: e0262577-e0262577

    • DOI

      10.1371/journal.pone.0262577

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of CREB Coactivator CRTC1 in SF1 Cells Leads to Hyperphagia and Obesity by High-fat Diet But Not Normal Chow Diet2021

    • Author(s)
      Matsumura Shigenobu、Ishikawa Fuka、Sasaki Tsutomu、Terkelsen Mike Krogh、Ravnskjaer Kim、Jinno Tomoki、Tanaka Jin、Goto Tsuyoshi、Inoue Kazuo
    • Journal Title

      Endocrinology

      Volume: 162 Issue: 9

    • DOI

      10.1210/endocr/bqab076

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Activation of the adipocyte CREB/CRTC pathway in obesity2021

    • Author(s)
      Yoon Young-Sil、Liu Weiyi、Van de Velde Sam、Matsumura Shigenobu、Wiater Ezra、Huang Ling、Montminy Marc
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1

    • DOI

      10.1038/s42003-021-02735-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] CREB coactivator CRTC1欠損マウスは高脂肪食摂取により糖尿病を発症する2019

    • Author(s)
      松村成暢
    • Organizer
      第24回 アディポサイエンスシンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited

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Published: 2019-04-18   Modified: 2024-01-30  

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