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New developments in basic and applied adiponectin research toward reduction of dementia risk and realization of healthy longevity

Research Project

Project/Area Number 19H01052
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Kadowaki Takashi  東京大学, 医学部附属病院, 客員研究員 (30185889)

Co-Investigator(Kenkyū-buntansha) 岩部 美紀  東京大学, 医学部附属病院, 特任准教授 (70392529)
岩部 真人  東京大学, 医学部附属病院, 准教授 (30557236)
山内 敏正  東京大学, 医学部附属病院, 教授 (40372370)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥45,890,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥10,590,000)
Fiscal Year 2021: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2020: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2019: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Keywordsアディポネクチン / アディポネクチン受容体 / 健康長寿 / 認知症 / 糖尿病合併症
Outline of Research at the Start

アディポネクチン及びその受容体(AdipoR)の作用が肥満に伴い低下することにより、メタボリックシンドローム・2型糖尿病・動脈硬化症が引き起こされる。本課題では、AdipoRの新規シグナル伝達機構の全容とAdipoRの糖脂質代謝・細胞ストレス改善における生物学的意義を解明し、受容体研究のブレイクスルーを目指す。また、認知症・動脈硬化症などの糖尿病合併症に対するAdipoRの抑制作用とそのメカニズムを解明する。さらに、AdipoRの立体構造・機能情報に基づいたAdipoR活性化低分子化合物の最適化や抗体医薬の開発による認知症などの多彩な合併症の抑制と健康長寿実現への基盤となる研究を展開する。

Outline of Final Research Achievements

Given that the action of adiponectin and its receptors (AdipoRs) is shown to become diminished with the onset of obesity leading to the onset of metabolic syndrome, type 2 diabetes, and atherosclerosis. This research project has aimed to achieve new breakthroughs in AdipoR research through elucidation of novel mechanisms of action of AdipoR signal transduction and their biological implications in glucose/lipid metabolism as well as cell stress reduction. This promoted fundamental drug discovery research leading to the reduction of diabetic complications, such as dementia and atherosclerosis.

Academic Significance and Societal Importance of the Research Achievements

糖尿病と合併症は、世界で激増しており、その原因解明と予防法・治療法開発は、喫緊の課題である。糖尿病は、細小血管症(網膜症、腎症、神経障害)や大血管症に加え、認知症やがんなどとも密接な関連が明らかとなってきた。これら多彩な合併症によって、健康寿命が短縮している。従って、動脈硬化症、特に認知症などの糖尿病合併症の病態解明と効果的な治療法開発は、超高齢社会において重要な課題であり、本研究成果の学術的意義および社会的意義は高いと考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Comments on the Screening Results   Annual Research Report
  • Research Products

    (39 results)

All 2022 2021 2020 2019

All Journal Article (19 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 19 results,  Open Access: 15 results) Presentation (12 results) (of which Int'l Joint Research: 7 results,  Invited: 12 results) Book (8 results)

  • [Journal Article] Elucidating exercise-induced skeletal muscle signaling pathways and applying relevant findings to preemptive therapy for lifestyle-related diseases2022

    • Author(s)
      Iwabu Masato、Okada-Iwabu Miki、Kadowaki Takashi、Yamauchi Toshimasa
    • Journal Title

      Endocrine Journal

      Volume: 69 Issue: 1 Pages: 1-8

    • DOI

      10.1507/endocrj.EJ21-0294

    • NAID

      130008145270

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Midlobular zone 2 hepatocytes: A gatekeeper of liver homeostasis2021

    • Author(s)
      Kubota Naoto、Kubota Tetsuya、Kadowaki Takashi
    • Journal Title

      Cell Metabolism

      Volume: 33 Issue: 5 Pages: 855-856

    • DOI

      10.1016/j.cmet.2021.04.005

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genotype-Structure-Phenotype Correlations of Disease-Associated IGF1R Variants and Similarities to Those of INSR Variants2021

    • Author(s)
      Hosoe Jun、Kawashima-Sonoyama Yuki、Miya Fuyuki、Kadowaki Hiroko、Suzuki Ken、Kato Takashi、Matsuzawa Fumiko、Aikawa Sei-Ichi、Okada Yukinori、Tsunoda Tatsuhiko、Hanaki Keiichi、Kanzaki Susumu、Shojima Nobuhiro、Yamauchi Toshimasa、Kadowaki Takashi
    • Journal Title

      Diabetes

      Volume: 70 Issue: 8 Pages: 1874

    • DOI

      10.2337/db20-1145

    • URL

      https://pure.teikyo.jp/en/publications/7726b5d1-1a8d-4046-bbfc-093c7eb261c9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preparation and culture of bone marrow-derived macrophages from mice for functional analysis.2021

    • Author(s)
      Gotaro Toda, Toshimasa Yamauchi, Takashi Kadowaki, and Kohjiro Ueki
    • Journal Title

      STAR Protocols

      Volume: 2 Issue: 1 Pages: 100246-100246

    • DOI

      10.1016/j.xpro.2020.100246

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice2021

    • Author(s)
      Iwabu Masato、Okada-Iwabu Miki、Tanabe Hiroaki、Ohuchi Nozomi、Miyata Keiko、Kobori Toshiko、Odawara Sara、Kadowaki Yuri、Yokoyama Shigeyuki、Yamauchi Toshimasa、Kadowaki Takashi
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 45-45

    • DOI

      10.1038/s42003-020-01579-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin- and Lipopolysaccharide-Mediated Signaling in Adipose Tissue Macrophages Regulates Postprandial Glycemia through Akt-mTOR Activation2020

    • Author(s)
      Toda G、Soeda K、Okazaki Y、Kobayashi N、Masuda Y、Arakawa N、Suwanai H、Masamoto Y、Izumida Y、Kamei N、Sasako T、Suzuki R、Kubota T、Kubota N、Kurokawa M、Tobe K、Noda T、Honda K、Accili D、Yamauchi T、Kadowaki T、Ueki K
    • Journal Title

      Molecular Cell

      Volume: 79 Issue: 1 Pages: 1-2

    • DOI

      10.1016/j.molcel.2020.04.033

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human adiponectin receptor AdipoR1 assumes closed and open structures2020

    • Author(s)
      Tanabe Hiroaki、Fujii Yoshifumi、Okada-Iwabu Miki、Iwabu Masato、Kano Kuniyuki、Kawana Hiroki、Hato Masakatsu、Nakamura Yoshihiro、Terada Takaho、Kimura-Someya Tomomi、Shirouzu Mikako、Kawano Yoshiaki、Yamamoto Masaki、Aoki Junken、Yamauchi Toshimasa、Kadowaki Takashi、Yokoyama Shigeyuki
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 446-446

    • DOI

      10.1038/s42003-020-01160-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NFIA differentially controls adipogenic and myogenic gene program through distinct pathways to ensure brown and beige adipocyte differentiation2020

    • Author(s)
      Hiraike Yuta、Waki Hironori、Miyake Kana、Wada Takahito、Oguchi Misato、Saito Kaede、Tsutsumi Shuichi、Aburatani Hiroyuki、Yamauchi Toshimasa、Kadowaki Takashi
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 9 Pages: e1009044-e1009044

    • DOI

      10.1371/journal.pgen.1009044

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical usefulness of multigene screening with phenotype-driven bioinformatics analysis for the diagnosis of patients with monogenic diabetes or severe insulin resistance2020

    • Author(s)
      Hosoe Jun, ... Fujiwara Toyofumi et al.
    • Journal Title

      Diabetes Research and Clinical Practice

      Volume: 169 Pages: 108461-108461

    • DOI

      10.1016/j.diabres.2020.108461

    • URL

      https://pure.teikyo.jp/en/publications/dea651fe-6a36-4497-9fe9-c7e624eef160

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blood Glucose Control Strategy for Type 2 Diabetes Patients With COVID-192020

    • Author(s)
      Futatsugi Hiroyuki、Iwabu Masato、Okada-Iwabu Miki、Okamoto Koh、Amano Yosuke、Morizaki Yutaka、Kadowaki Takashi、Yamauchi Toshimasa
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 7 Pages: 593061-593061

    • DOI

      10.3389/fcvm.2020.593061

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients2020

    • Author(s)
      Enooku K, Tsutsumi T, Kondo M, Fujiwara N, Sasako T, Shibahara J, Kado A, Okushin K, Fujinaga H, Nakagomi R, Minami T, Sato M, Uchino K, Nakagawa H, Kondo Y, Asaoka Y, Tateishi R, Ueki K, Ikeda H, Yoshida H, Moriya K, Yotsuyanagi H, Kadowaki T, Koike K
    • Journal Title

      J Gastroenterol

      Volume: 55 Issue: 2 Pages: 227

    • DOI

      10.1007/s00535-019-01633-2

    • URL

      https://pure.teikyo.jp/en/publications/e52a22bc-2c45-40d7-8f11-787d7daeef17

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolyl Hydroxylase Domain Inhibitor Protects against Metabolic Disorders and Associated Kidney Disease in Obese Type 2 Diabetic Mice2020

    • Author(s)
      Mai Sugahara、Shinji Tanaka、Tetsuhiro Tanaka、Hisako Saito、Yu Ishimoto、Takeshi Wakashima、Masatoshi Ueda、Kenji Fukui、Akira Shimizu、Reiko Inagi、Toshimasa Yamauchi、Takashi Kadowaki、Masaomi Nangaku
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: 31 Issue: 3 Pages: 560-577

    • DOI

      10.1681/asn.2019060582

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug development research for novel adiponectin receptor-targeted antidiabetic drugs contributing to healthy longevity2019

    • Author(s)
      Okada-Iwabu Miki、Iwabu Masato、Yamauchi Toshimasa、Kadowaki Takashi
    • Journal Title

      DIABETOLOGY INTERNATIONAL

      Volume: 10 Issue: 4 Pages: 237-244

    • DOI

      10.1007/s13340-019-00409-6

    • NAID

      40022039924

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adiponectin/AdipoR Research and Its Implications for Lifestyle-Related Diseases2019

    • Author(s)
      Iwabu Masato、Okada-Iwabu Miki、Yamauchi Toshimasa、Kadowaki Takashi
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 6 Pages: 116-116

    • DOI

      10.3389/fcvm.2019.00116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NAD + supplementation rejuvenates aged gut adult stem cells2019

    • Author(s)
      Igarashi M*, Miura M, Williams E, Jaksch F, Kadowaki T, Yamauchi T* , Guarente L
    • Journal Title

      Aging Cell

      Volume: - Issue: 3 Pages: 1-10

    • DOI

      10.1111/acel.12935

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential effects of diet- and genetically-induced brain insulin resistance on amyloid pathology in a mouse model of Alzheimer’s disease2019

    • Author(s)
      Tomoko Wakabayashi, Kazuki Yamaguchi, Kentaro Matsui, Toshiharu Sano, Tetsuya Kubota, Tadafumi Hashimoto, Ayako Mano, Kaoru Yamada, Yuko Matsuo, Naoto Kubota, Takashi Kadowaki, Takeshi Iwatsubo
    • Journal Title

      Molecular Neurodegeneration

      Volume: 14 Issue: 1 Pages: 15-15

    • DOI

      10.1186/s13024-019-0315-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Robust and highly efficient hiPSC generation from patient non-mobilized peripheral blood-derived CD34+ cells using the auto-erasable Sendai virus vector.2019

    • Author(s)
      Okumura T, Horie Y, et al.
    • Journal Title

      Stem Cell Res Ther.

      Volume: 10 Issue: 1 Pages: 185-185

    • DOI

      10.1186/s13287-019-1273-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pivotal role of inter-organ aspartate metabolism for treatment of mitochondrial aspartate-glutamate carrier 2 (citrin) deficiency, based on the mouse model.2019

    • Author(s)
      Saheki T, Moriyama M, Kuroda E, Funahashi A, Yasuda I, Setogawa Y, Gao Q, Ushikai M, Furuie S, Yamamura KI, Takano K, Nakamura Y, Eto K, Kadowaki T, Sinasac DS, Furukawa T, Horiuchi M, Tai YH.
    • Journal Title

      Sci Rep. 2019 Mar 12;9(1):4179.

      Volume: 9 (1) Issue: 1 Pages: 4179-4179

    • DOI

      10.1038/s41598-019-39627-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Molecular mechanism of insulin resistance and comorbidities linked to obesity2021

    • Author(s)
      Kadowaki T
    • Organizer
      Asia-Oceania Conference on Obesity and Malaysian Association for Study of Obesity Scientific Conference (AOCO-MASO2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanism of obesity-linked insulin resistance and type 2 diabetes2021

    • Author(s)
      Kadowaki T
    • Organizer
      Sabri Ulker Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 2型糖尿病 ―成因と治療の最新知見2021

    • Author(s)
      門脇 孝
    • Organizer
      第22回日本内分泌学会中国支部学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanism of Thyoe 2 Diabetes and Insulin Resistance2021

    • Author(s)
      Takashi Kadowaki
    • Organizer
      TORONTO VIRTUAL PRESENTATION AT CITY-WIDE ENDOCRINE ROUNDS
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 理事長提言2021

    • Author(s)
      門脇 孝
    • Organizer
      第41回 日本肥満学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanism of obesity-linked comorbidities2020

    • Author(s)
      Takashi Kadowaki
    • Organizer
      International Congress on Obesity and Metabolic Syndrome
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] What is type 2 diabetes? A long journey to seek the truth2020

    • Author(s)
      Takashi Kadowaki
    • Organizer
      56th EASD Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 糖尿病学会への提言2020

    • Author(s)
      門脇 孝
    • Organizer
      第63回 日本糖尿病学会年次学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 糖尿病・代謝学の展望2020

    • Author(s)
      門脇 孝
    • Organizer
      第30回 臨床内分泌代謝Update
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 2型糖尿病治療の現状と将来展望2019

    • Author(s)
      門脇 孝
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Adiponectin receptor (AdipoR) and skeletal muscle Akt.2019

    • Author(s)
      Takashi Kadowaki
    • Organizer
      Regulators of anti-aging : Cold Spring Harbor Laboratory Meeting Mechanisms of Metabolic Signaling
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Elucidation of roles of insulin resistance and decreased adiponectin action in type 2 diabetes and diabetes complications and development of their therapeutic strategy2019

    • Author(s)
      Takashi Kadowaki
    • Organizer
      International Diabetes Federation 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 「特別企画:Claude Bernard賞を受賞して」糖尿病学20212021

    • Author(s)
      門脇 孝
    • Total Pages
      155
    • Publisher
      株式会社 診断と治療社
    • Related Report
      2021 Annual Research Report
  • [Book] 「序文」糖尿病学20212021

    • Author(s)
      門脇 孝、山内 敏正
    • Total Pages
      155
    • Publisher
      株式会社 診断と治療社
    • Related Report
      2021 Annual Research Report
  • [Book] 「アディポネクチン受容体の新たな構造」糖尿病学20212021

    • Author(s)
      岩部 美紀、岩部 真人、山内 敏正、門脇 孝
    • Total Pages
      155
    • Publisher
      株式会社 診断と治療社
    • Related Report
      2021 Annual Research Report
  • [Book] 特集 肥満症をめぐる最近の話題 序文 医学と薬学2021

    • Author(s)
      門脇 孝
    • Total Pages
      96
    • Publisher
      自然科学社
    • Related Report
      2020 Annual Research Report
  • [Book] セミナーII 糖尿病の管理・治療のドリーム 糖尿病UP・DATE 賢島セミナー 20192020

    • Author(s)
      門脇 孝
    • Total Pages
      247
    • Publisher
      メディカル・ジャーナル社
    • Related Report
      2020 Annual Research Report
  • [Book] 巻頭言 Obesity stigma BIO Clinica2020

    • Author(s)
      門脇 孝
    • Total Pages
      98
    • Publisher
      北隆館
    • Related Report
      2020 Annual Research Report
  • [Book] PROGRESS IN MEDICINE:【SGLT2阻害薬Update】2020

    • Author(s)
      門脇 孝
    • Total Pages
      91
    • Publisher
      株式会社メテオ
    • Related Report
      2019 Annual Research Report
  • [Book] 糖尿病UP-DATE:【臨床研究から日常診療へのシームレスな活用】 臨床研究に学ぶ糖尿病治療の現況と展望2019

    • Author(s)
      門脇 孝
    • Total Pages
      256
    • Publisher
      株式会社 メディカル・ジャーナル社
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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