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Autonomic nerve-mediated regulation of adipose tissue metabolism: parasympathetic nervous system and adiponectin secretion

Research Project

Project/Area Number 21K19496
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Kubota Naoto  東京大学, 医学部附属病院, 届出研究員 (50396719)

Co-Investigator(Kenkyū-buntansha) 窪田 哲也  公益財団法人朝日生命成人病研究所, その他部局等, 教授(移行) (60385698)
相原 允一  東京大学, 医学部附属病院, 助教 (60779362)
Project Period (FY) 2021-07-09 – 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 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsアディポネクチン / 糖尿病
Outline of Research at the Start

アディポネクチン(Ad)はインスリン感受性ホルモンとして同定され、肥満に伴う分泌低下がインスリン抵抗性の原因の1つと考えられているが、その分泌調節機構は今なお十分に解明されていない。本研究は、長年課題とされてきた“Adの生理的な分泌調節機構とその破綻の分子メカニズム”を解明しようとするものである。肥満では通常Adは低下するが、本研究では視床下部腹内側核(VMH)の破壊により肥満を呈するにもかかわらず、むしろAdが増加するということを見出しており、これは肥満とは独立にAd分泌が自律神経によって制御されていることを強く示唆しており、その分子メカニズムの解明は卓越した成果が期待できる。

Outline of Final Research Achievements

Adiponectin has been identified as an insulin-sensitive hormone, and its decrease with obesity is thought to be causes of insulin resistance, but the regulatory mechanism is still not fully understood. In this study, we found that adiponectin is increased in a model of disrupted hypothalamic ventral medial nucleus (VMH) despite the presence of obesity, indicating that adiponectin secretion is regulated by the autonomic nervous system. The expression of PPARγ and FGF21 was upregulated in the adipose tissue of VMH-disrupted mice, suggesting that these molecules regulate adiponectin secretion independently of obesity.

Academic Significance and Societal Importance of the Research Achievements

インスリン感受性ホルモンであるアディポネクチンが抗糖尿病作用・抗動脈硬化作用を有していることに関しては既に国内外から数多くの報告があったが、その分泌調節機構や病態における破綻のメカニズムについてはなお十分な知見が得られていなかった。本研究は、長年課題とされてきた“アディポネクチンの生理的な分泌調節機構とその破綻の分子メカニズム”の一端を解明し、新規肥満インスリン抵抗性治療開発につながる可能性がある。

Report

(3 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (18 results)

All 2022 2021

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (7 results) (of which Invited: 7 results) Book (4 results)

  • [Journal Article] A Case of Chronic Intestinal Pseudo-obstruction with Mitochondrial Diseases.2022

    • Author(s)
      Jinnouchi T, Sakurai Y, Miyoshi K, Koizumi C, Waki H, Kubota N, Yamauchi T.
    • Journal Title

      Intern. Med.

      Volume: 61 Pages: 469-474

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The sodium-glucose co-transporter 2 inhibitor tofogliflozin suppresses atherosclerosis through glucose lowering in ApoE-deficient mice with streptozotocin-induced diabetes.2022

    • Author(s)
      Iwamoto M, Kubota T, Sakurai Y, Wada N, Shioda S, Yamauchi T, Kadowaki T, Kubota N
    • Journal Title

      Pharmacol. Res. Perspect.

      Volume: 10

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men.2022

    • Author(s)
      Igarashi M, Nakagawa-Nagahama Y, Miura M, Kashiwabara K, Yaku K, Sawada M, Sekine R, Fukamizu Y, Sato T, Sakurai T, Sato J, Ino K, Kubota N, Nakagawa T, Kadowaki T & Yamauchi T.
    • Journal Title

      npj Aging

      Volume: 8 Pages: 5-5

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stool pattern is associated with not only the prevalence of tumorigenic bacteria isolated from fecal matter but also plasma and fecal fatty acids in healthy Japanese adults2021

    • Author(s)
      Watanabe Daiki、Murakami Haruka、Ohno Harumi、Tanisawa Kumpei、Konishi Kana、Todoroki-Mori Kikue、Tsunematsu Yuta、Sato Michio、Ogata Yuji、Miyoshi Noriyuki、Kubota Naoto、Kunisawa Jun、Wakabayashi Keiji、Kubota Tetsuya、Watanabe Kenji、Miyachi Motohiko
    • Journal Title

      BMC Microbiology

      Volume: 21 Issue: 1 Pages: 196-196

    • DOI

      10.1186/s12866-021-02255-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lack of Brain Insulin Receptor Substrate-1 Causes Growth Retardation, With Decreased Expression of Growth Hormone?Releasing Hormone in the Hypothalamus2021

    • Author(s)
      Hayashi Takanori、Kubota Tetsuya、Mariko Inoue、Takamoto Iseki、Aihara Masakazu、Sakurai Yoshitaka、Wada Nobuhiro、Miki Takashi、Yamauchi Toshimasa、Kubota Naoto、Kadowaki Takashi
    • Journal Title

      Diabetes

      Volume: 70 Issue: 8 Pages: 1640-1653

    • DOI

      10.2337/db20-0482

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein intake after the initiation of chemotherapy is an independent prognostic factor for overall survival in patients with unresectable pancreatic cancer: A prospective cohort study2021

    • Author(s)
      Hasegawa Yoko、Ijichi Hideaki、Saito Kei、Ishigaki Kazunaga、Takami Maki、Sekine Rie、Usami Satoshi、Nakai Yousuke、Koike Kazuhiko、Kubota Naoto
    • Journal Title

      Clinical Nutrition

      Volume: 40 Issue: 7 Pages: 4792-4798

    • DOI

      10.1016/j.clnu.2021.06.011

    • Related Report
      2021 Research-status Report
  • [Journal Article] A xanthene derivative, DS20060511, attenuates glucose intolerance by inducing skeletal muscle-specific GLUT4 translocation in mice2021

    • Author(s)
      Furuzono Shinji、Kubota Tetsuya、Taura Junki、Konishi Masahiro、Naito Asuka、Tsutsui Masato、Karasawa Hiroshi、Kubota Naoto、Kadowaki Takashi
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 994-994

    • DOI

      10.1038/s42003-021-02491-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 2型糖尿病への臨床栄養学の進歩 糖尿病の食事療法 最新の知見も含めて2022

    • Author(s)
      窪田直人
    • Organizer
      第44回日本臨床栄養学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 2型糖尿病の病態と薬物治療2022

    • Author(s)
      窪田直人
    • Organizer
      第67回日本内科学会信越支部生涯教育講演会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 肥満症の食事療法・栄養指導2022

    • Author(s)
      窪田直人
    • Organizer
      第43回日本肥満学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 肥満2型糖尿病における栄養療法を考える:肥満2型糖尿病における栄養療法の現状と課題2021

    • Author(s)
      窪田直人
    • Organizer
      第41回日本肥満学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 脂肪細胞+炎症:肥満におけるM2マクロファージ活性化障害機構2021

    • Author(s)
      窪田哲也
    • Organizer
      第41回日本肥満学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] ヒトの腸内細菌叢とインスリン抵抗性におけるMulti-Omics解析2021

    • Author(s)
      窪田直人
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 糖尿病の病態-immunometabolism(免疫代謝学)からのアプローチ高インスリン血症によるM2マクロファージ活性化障害2021

    • Author(s)
      窪田哲也
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Book] 医学のあゆみ2021

    • Author(s)
      窪田直人,窪田哲也,門脇孝
    • Total Pages
      7
    • Publisher
      医歯薬出版
    • Related Report
      2021 Research-status Report
  • [Book] 月刊糖尿病ライフ2021

    • Author(s)
      窪田直人
    • Total Pages
      4
    • Publisher
      日本糖尿病協会
    • Related Report
      2021 Research-status Report
  • [Book] 月刊糖尿病2021

    • Author(s)
      澤田実佳,窪田 直人
    • Total Pages
      7
    • Publisher
      医学出版
    • Related Report
      2021 Research-status Report
  • [Book] Medical Practice2021

    • Author(s)
      林高則,窪田直人
    • Total Pages
      7
    • Publisher
      文光堂
    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-07-13   Modified: 2025-01-30  

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