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Elucidation of the mechanism of hypothermia induced by a newly discovered hypothalamic small protein

Research Project

Project/Area Number 19K06768
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
Research InstitutionHiroshima University

Principal Investigator

Iwakoshi Eiko  広島大学, 統合生命科学研究科(総), 特任准教授 (50311296)

Project Period (FY) 2019-04-01 – 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 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords視床下部 / 熱産生 / 褐色脂肪組織 / 神経ペプチド / 分泌性小タンパク質 / 脂肪蓄積 / 熱産生能 / 遺伝子改変動物
Outline of Research at the Start

研究代表者は新規分泌性小タンパク質neurosecretory protein GL(NPGL)とneurosecretory protein GM(NPGM)の機能解析を進めている。哺乳類を用いた先行研究からNPGLが脂肪蓄積を促すことを見出している。さらに、交感神経活動を低下させ、褐色脂肪組織の機能低下を引き起こしている可能性がある。本研究では、NPGLやNPGM産生細胞の神経ネットワークの解析、熱産生低下への寄与、分子メカニズムの解明を目指す。そのために、形態学的解析、低温環境曝露処理、遺伝子改変動物での熱産生能力の解析等を行い、NPGLやNPGMの生理作用や生理的意義を明らかにする。

Outline of Final Research Achievements

We have discovered a novel small secretory protein, NPGL, in the hypothalamus. Previous studies in rodents have found that NPGL promotes fat accumulation in white adipose tissue. The purpose of this study was to investigate the effect of NPGL on reducing thermogenesis in rodents. In this study, we found that NPGL decreased thermogenesis through fat synthesis and fat accumulation in brown adipose tissue. Morphological analysis revealed that approximately 50% of NPGL-producing cells were GABAergic neurons. This study shows that NPGL produced in the hypothalamus has the function of lowering energy expenditure and thermogenesis.

Academic Significance and Societal Importance of the Research Achievements

我々ヒトを含めた哺乳類は恒温度物であり、体温調節は極めて重要である。体温調節の制御理解は、熱中症や低体温症の対策・予防にも繋がる。研究代表者らが発見した新規脳因子のNPGLは脂肪蓄積や肥満などに関わることを見出していたが、本研究の遂行により、褐色脂肪組織の熱産生を抑制していることが明らかになった。本研究成果は、エネルギー代謝調節機構の解明へ重要な新知見を加えたため、学術的にも社会的にも大きな意義を持つ研究であると考えている。

Report

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

    (13 results)

All 2022 2021 2020 2019

All Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Neurosecretory Protein GL Promotes Normotopic Fat Accumulation in Male ICR Mice2022

    • Author(s)
      Yuki Narimatsu, Daichi Matsuura, Eiko Iwakoshi-Ukena, Megumi Furumitsu, Kazuyoshi Ukena
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 12 Pages: 6488-6488

    • DOI

      10.3390/ijms23126488

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypothalamic Overexpression of Neurosecretory Protein GL Leads to Obesity in Male C57BL/6J Mice2022

    • Author(s)
      Narimatsu Yuki、Iwakoshi-Ukena Eiko、Fukumura Keisuke、Shikano Kenshiro、Furumitsu Megumi、Morishita Masahiro、Bentley George E.、Kriegsfeld Lance J.、Ukena Kazuyoshi
    • Journal Title

      Neuroendocrinology

      Volume: - Issue: 6 Pages: 606-620

    • DOI

      10.1159/000518969

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunohistochemical Analysis of Neurotransmitters in Neurosecretory Protein GL-Producing Neurons of the Mouse Hypothalamus2022

    • Author(s)
      Naito Mana、Iwakoshi-Ukena Eiko、Moriwaki Shogo、Narimatsu Yuki、Kato Masaki、Furumitsu Megumi、Miyamoto Yuta、Esumi Shigeyuki、Ukena Kazuyoshi
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 2 Pages: 454-454

    • DOI

      10.3390/biomedicines10020454

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neurosecretory Protein GL Accelerates Liver Steatosis in Mice Fed Medium-Fat/Medium-Fructose Diet2022

    • Author(s)
      Narimatsu Yuki、Iwakoshi-Ukena Eiko、Naito Mana、Moriwaki Shogo、Furumitsu Megumi、Ukena Kazuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 4 Pages: 2071-2071

    • DOI

      10.3390/ijms23042071

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of neurosecretory protein GL on food intake and fat accumulation under different dietary nutrient compositions in rats2021

    • Author(s)
      Fukumura Keisuke、Shikano Kenshiro、Narimatsu Yuaki、Iwakoshi-Ukena Eiko、Furumitsu Megumi、Naito Mana、Ukena Kazuyoshi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: zbab064 Issue: 6 Pages: 1514-1520

    • DOI

      10.1093/bbb/zbab064

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Overexpression of Neurosecretory Protein GL-Precursor Gene on Glucose Homeostasis and Insulin Sensitivity in Mice2021

    • Author(s)
      Fukumura Keisuke、Narimatsu Yuki、Moriwaki Shogo、Iwakoshi-Ukena Eiko、Furumitsu Megumi、Ukena Kazuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 9 Pages: 4681-4681

    • DOI

      10.3390/ijms22094681

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of the Gene Encoding Neurosecretory Protein GL Precursor Prevents Excessive Fat Accumulation in the Adipose Tissue of Mice Fed a Long-Term High-Fat Diet2021

    • Author(s)
      Fukumura Keisuke、Narimatsu Yuki、Moriwaki Shogo、Iwakoshi-Ukena Eiko、Furumitsu Megumi、Ukena Kazuyoshi
    • Journal Title

      Molecules

      Volume: 26 Issue: 19 Pages: 6006-6006

    • DOI

      10.3390/molecules26196006

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Irregular Feeding on the Daily Fluctuations in mRNA Expression of the Neurosecretory Protein GL and Neurosecretory Protein GM Genes in the Mouse Hypothalamus2021

    • Author(s)
      Kadota Atsuki、Iwakoshi-Ukena Eiko、Fukumura Keisuke、Shikano Kenshiro、Narimatsu Yuki、Furumitsu Megumi、Ukena Kazuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 4 Pages: 2109-2109

    • DOI

      10.3390/ijms22042109

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Chronic Intracerebroventricular Infusion of RFamide-Related Peptide-3 on Energy Metabolism in Male Mice2020

    • Author(s)
      Moriwaki Shogo、Narimatsu Yuki、Fukumura Keisuke、Iwakoshi-Ukena Eiko、Furumitsu Megumi、Ukena Kazuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 22 Pages: 8606-8606

    • DOI

      10.3390/ijms21228606

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neurosecretory protein GL induces fat accumulation in mice.2020

    • Author(s)
      Shikano K, Iwakoshi-Ukena E, Saito T, Narimatsu Y, Kadota A, Furumitsu M, Bentley GE, Kriegsfeld LJ, Ukena K.
    • Journal Title

      J. Endocrinol.

      Volume: 244 Issue: 1 Pages: 1-12

    • DOI

      10.1530/joe-19-0112

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neurosecretory protein GL induces fat accumulation in chicks.2019

    • Author(s)
      Shikano K, Iwakoshi-Ukena E, Kato M, Furumitsu M, Bentley GE, Kriegsfeld LJ, Ukena K.
    • Journal Title

      Front. Endocrinol.

      Volume: 10 Pages: 392-392

    • DOI

      10.3389/fendo.2019.00392

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 視床下部分泌性小タンパク質の脂肪蓄積作用2020

    • Author(s)
      福村圭介、成松勇樹、鹿野健史朗、齋藤鷹也、近藤邦裕、 古満芽久美、岩越栄子、浮穴和義
    • Organizer
      第5回食欲・食嗜好の分子・神経基盤研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] エネルギー代謝調節に関わる新規神経ペプチドの発見と機能解析2019

    • Author(s)
      浮穴和義、岩越栄子
    • Organizer
      日本動物学会 第90回大阪大会  第4回ペプチド・ホルモン研究会シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited

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

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