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Mechanisms of interaction between age-dependent obesity and localization of melanocoretin-4 receptors

Research Project

Project/Area Number 17K15571
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Research InstitutionNagoya University

Principal Investigator

Oya Manami  名古屋大学, 医学系研究科, 学振特別研究員(RPD) (90777997)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsメラノコルチン / 生理学 / 肥満 / 加齢 / 代謝調節 / 摂食制御 / 視床下部背内側部
Outline of Final Research Achievements

Obesity is often developed with age due to attenuation of energy expenditure including metabolic thermogenesis. However, the mechanism of age-dependent attenuation of whole-body metabolism is unknown. In this study, we focused on melanocortin-4 receptors (MC4Rs), which play essential roles in the regulation of the central neural circuit controlling metabolic thermogenesis in brown adipose tissue (BAT). Our in vivo physiological experiments revealed that skin cooling-induced BAT thermogenesis and MC4R agonist-induced BAT thermogenesis were attenuated in older (6 months old) male rats compared with younger (9 weeks old) ones. To elucidate the mechanism of the age-dependent attenuation of MC4R sensitivity to melanocortin signals, we examined the distribution of MC4Rs. We found that aging changes the localization of MC4Rs. Thus, we hypothesized that age-dependent alteration in the localization of MC4R induces attenuation of MC4R sensitivity in older animals.

Academic Significance and Societal Importance of the Research Achievements

飽食と高齢化が進む現代において、加齢による肥満の発症機構の解明は重要な課題である。加齢性肥満の発症の原因の一つとして代謝量の減少が考えられるが、加齢による代謝量の低下メカニズムは明らかにされていない。本研究によってMC4Rを介した摂食・代謝調節機構が加齢によって変化するメカニズムを分子レベルで解明することが出来れば、これまでに考えられていなかった新しい肥満発症機構の提示につながるだけでなく、MC4Rの局在の制御を通じた画期的な肥満予防法や治療法の開発に寄与できると考える。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2020 2019 2018

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

  • [Journal Article] Combi-CRISPR: combination of NHEJ and HDR provides efficient and precise plasmid-based knock-ins in mice and rats2020

    • Author(s)
      Yoshimi K, Oka Y, Miyasaka Y, Kotani Y, Yasumura M, Uno Y, Hattori K, Tanigawa A, Sato M, Oya M, Nakamura K, Matsushita N, Kobayashi K, Mashimo T
    • Journal Title

      Hum Genet

      Volume: 140 Issue: 2 Pages: 277-287

    • DOI

      10.1007/s00439-020-02198-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 加齢性肥満発症機構の解明を目指した抗メラノコルチン4型受容体抗体の作製2020

    • Author(s)
      大屋 愛実
    • Organizer
      日本生理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Age-dependent attenuation of hypothalamic sensitivity to thermogenic melanocortin signals.2019

    • Author(s)
      大屋 愛実
    • Organizer
      第9回FAOPS congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 視床下部メラノコルチン受容体を介した熱産生反応は加齢とともに減弱する2018

    • Author(s)
      大屋 愛実
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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