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Elucidation of the obesity paradox and the desire for exercise through the effects of a novel brain factor

Research Project

Project/Area Number 20K21760
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionHiroshima University

Principal Investigator

Ukena Kazuyoshi  広島大学, 統合生命科学研究科(総), 教授 (10304370)

Co-Investigator(Kenkyū-buntansha) 岩越 栄子  広島大学, 統合生命科学研究科(総), 特任准教授 (50311296)
福村 圭介  広島大学, 統合生命科学研究科(総), 助教 (10880049)
Project Period (FY) 2020-07-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords新規脳因子 / 小タンパク質 / 肥満パラドックス / 脂肪蓄積 / 骨格筋 / 運動 / エネルギー代謝 / 標的組織 / 受容体 / 運動欲求性 / 白色脂肪組織 / 遅筋線維
Outline of Research at the Start

過体重の方が生命予後に有利に働くという「肥満パラドックス」が存在する。研究代表者らが発見した新規脳因子であるNPGLは、運動が制限された状態では脂肪蓄積を亢進させるが、血糖値や血中脂質濃度を上昇させない。本研究では、NPGLが肥満パラドックス形成の要の因子であると考え、白色脂肪組織における脂質代謝関連遺伝子発現量、脂肪酸含有量、異所性脂肪蓄積や血中脂質濃度上昇の防止機構を解明し、更には、運動欲求性を高める可能性を検証することを目的とする。

Outline of Final Research Achievements

We have found that a hypothalamic factor, neurosecretory protein GL (NPGL), causes overeating and obesity in rodents. The purpose of this study is to clarify the possible involvement of NPGL in the formation mechanism of the obesity paradox, in which a healthy state is maintained even in the obese state. In this study, obese mice were generated by feeding a high-fat diet, and their body weight and fat mass were analyzed under conditions in which they were able to perform voluntary exercise on a rotating wheel. The results showed that NPGL activates energy metabolism in muscle and increases slow-twitch muscle fibers in obese mice, thereby increasing endurance and maintaining spontaneous locomotion.

Academic Significance and Societal Importance of the Research Achievements

肥満は万病と元とも言われ、昨今の先進国における飽食の時代には,糖尿病や高血圧症などの生活習慣病の原因とされている。一方で、動物における脂肪蓄積は、エネルギー貯蔵に加え、繁殖や生命維持に必要不可欠な生命現象である。さらに、肥満状態であっても良い健康状態を保っている肥満パラドックスも知られている。本研究では、新たに見出した脳因子のNPGLが作用すると、肥満状態であっても運動量の低下が生じず、骨格筋重量の増加や骨格筋中のエネルギー代謝が上昇することを見出した。つまり、NPGLが肥満パラドックスを誘導している可能性を示した。動物の脂肪蓄積と筋組織維持の制御メカニズムに新たな知見を加えることができた。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (17 results)

All 2023 2022 2021 2020

All Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results,  Open Access: 12 results) Presentation (3 results) (of which Invited: 2 results)

  • [Journal Article] Neurosecretory Protein GM-Expressing Neurons Participate in Lipid Storage and Inflammation in Newly Developed Cre Driver Male Mice2023

    • Author(s)
      Narimatsu Yuki、Kato Masaki、Iwakoshi-Ukena Eiko、Moriwaki Shogo、Ogasawara Ayano、Furumitsu Megumi、Ukena Kazuyoshi
    • Journal Title

      Biomedicines

      Volume: 11 Issue: 12 Pages: 3230-3230

    • DOI

      10.3390/biomedicines11123230

    • Related Report
      2023 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] Advancing reproductive neuroendocrinology through research on the regulation of GnIH and on its diverse actions on reproductive physiology and behavior2022

    • Author(s)
      Tsutsui Kazuyoshi、Ubuka Takayoshi、Ukena Kazuyoshi
    • Journal Title

      Frontiers in Neuroendocrinology

      Volume: 64 Pages: 100955-100955

    • DOI

      10.1016/j.yfrne.2021.100955

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [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] Effect of Stressors on the mRNA Expressions of Neurosecretory Protein GL and Neurosecretory Protein GM in Chicks2022

    • Author(s)
      Kato Masaki、Iwakoshi-Ukena Eiko、Narimatsu Yuki、Furumitsu Megumi、Ukena Kazuyoshi
    • Journal Title

      Frontiers in Physiology

      Volume: 13 Pages: 860912-860912

    • DOI

      10.3389/fphys.2022.860912

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adrenomedullin 2 and 5 activate the calcitonin receptor-like receptor (clr) – Receptor activity-modifying protein 3 (ramp3) receptor complex in Xenopus tropicalis2021

    • Author(s)
      Ogoshi M, Takahashi M, Aoyagi K, Ukena K, Aizawa S, Takeuchi H, Takahashi S, Takeuchi S.
    • Journal Title

      Gen Comp Endocrinol.

      Volume: 306 Pages: 113752-113752

    • DOI

      10.1016/j.ygcen.2021.113752

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [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] Subcutaneous infusion of neurosecretory protein GL promotes fat accumulation in mice2021

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

      Heliyon

      Volume: 7 Issue: 7 Pages: e07502-e07502

    • DOI

      10.1016/j.heliyon.2021.e07502

    • Related Report
      2021 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] A Novel Hypothalamic Factor, Neurosecretory Protein GM, Causes Fat Deposition in Chicks2021

    • Author(s)
      Kato Masaki、Iwakoshi-Ukena Eiko、Furumitsu Megumi、Ukena Kazuyoshi
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 747473-747473

    • DOI

      10.3389/fphys.2021.747473

    • Related Report
      2021 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
  • [Presentation] 新規神経ペプチドの同定と生理機能に関する研究2022

    • Author(s)
      浮穴和義
    • Organizer
      2022年日本動物学会学会賞受賞者講演
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 新規神経分泌因子の発見とその機能2021

    • Author(s)
      浮穴和義
    • Organizer
      第126回日本解剖学会総会・全国学術集会/第98回日本生理学会大会合同大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [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

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Published: 2020-08-03   Modified: 2025-01-30  

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