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Pathophysiolosy of insulin resistance in pregnancy in terms of the inter-organ networks

Research Project

Project/Area Number 19K09825
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionEhime University

Principal Investigator

SUGIYAMA TAKASHI  愛媛大学, 医学系研究科, 教授 (10263005)

Co-Investigator(Kenkyū-buntansha) 内倉 友香  愛媛大学, 医学系研究科, 助教 (50648623)
松原 裕子  愛媛大学, 医学部附属病院, 講師 (60403820)
高木 香津子  愛媛大学, 医学部附属病院, 助教 (80648626)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords妊娠 / 子宮内環境 / マウス / DOHaD / 食餌介入 / 肥満 / 高脂肪食 / インスリン抵抗性 / 臓器間ネットワーク
Outline of Research at the Start

妊娠後半期に生じるインスリン抵抗性は、胎児発育の視点からみると合目的的な現象といえる。一方、このインスリン抵抗性の発生機序に関しては、依然未解明な点が多い。その理由は、これまでの検討方法が臓器横断的な検討であったため、生体全体の反応としての把握がなされていなかった可能性があるからである。
本研究の目的は、臓器間ネットワークの視点より生体をよりグローバルに捉え、妊娠中における脳、自律神経(迷走神経、交感神経)、脂肪組織、肝臓、胎盤間のネットワークについて検討し、妊娠中に生じる生理的なインスリン抵抗性の発生機序を解明すると共に肥満等の過剰インスリン抵抗性が生じた際の治療戦略を立てることである。

Outline of Final Research Achievements

The long-term effect of changes in maternal dietary composition during pregnancy on the offspring's metabolic homeostasis is uncertain. We aimed to
investigate the long-term effects of maternal balanced low-fat interventions on metabolic homeostasis of the offspring using a mouse model of gestational
obesity induced by a high-fat diet (HFD). Changes in the intervention diet improved glucose tolerance in pups at 3 and 12 weeks of age. We also performed transcriptomic analysis of the liver in neonatal and 3-week-old pups. Genes in the peroxisome proliferator-activated receptor signaling pathway were significantly down-regulated in neonates in the intervention group compared with the HFD group. The interventio diet compensated for the detrimental effects of a maternal HFD on glucose and lipid metabolism in male offspring by changing the gene expression profile. These data suggest that maternal balanced low-fat intervention is critical for improving the metabolic health of offsprings.

Academic Significance and Societal Importance of the Research Achievements

肥満女性に対する妊娠中の食事介入が母体のみならず次世代に好影響を及ぼすことをマウスモデルを用いてエピジェネティックなメカニズムとともに明らかにすることができた。
今後、本モデルマウスを用いて予防や治療に関するさらなる方策を探ることができる点で学術的および社会的意義を有すると考えられた。

Report

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

    (14 results)

All 2022 2021 2020 2019

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Long-term impact of maternal dietary intervention on metabolic homeostasis in male offspring in mice2022

    • Author(s)
      Ueno M, Liu S, Kiyoi T, Mogi M, Sugiyama T
    • Journal Title

      J Nutr Biochem

      Volume: 104 Pages: 108971-108971

    • DOI

      10.1016/j.jnutbio.2022.108971

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perinatal low-fat dietary intervention affects glucose metabolism in female adult and aging offspring2022

    • Author(s)
      Ueno M, Liu S, Kiyoi T, Sugiyama T, Mogi M
    • Journal Title

      Geriatr Gerontol Int

      Volume: in press Issue: 5 Pages: 441-448

    • DOI

      10.1111/ggi.14378

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cesarean section is associated with increased risk of postpartum depressive symptoms in Japan: the Kyushu Okinawa Maternal and Child Health Study2021

    • Author(s)
      Yokoyama M, Tanaka K, Sugiyama T, Arakawa M, Miyake Y
    • Journal Title

      J Affect Disord

      Volume: 278 Pages: 497-501

    • DOI

      10.1016/j.jad.2020.09.106

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship Between Human β-Defensin 2 and the Vaginal Environment2020

    • Author(s)
      Kotani H, Koshizuka T, Matsubara K, Nishiyama K, Sugiyama T, Suzutani T
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 73 Issue: 3 Pages: 214-220

    • DOI

      10.7883/yoken.JJID.2019.190

    • NAID

      130007845524

    • ISSN
      1344-6304, 1884-2836
    • Year and Date
      2020-05-29
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of pregnancy outcomes between women with early-onset and late-onset gestational diabetes: A retrospective multi-institutional study in Japan.2020

    • Author(s)
      Usami T, Yokoyama M, Iwama N, Sagawa N, Hiramatsu Y, Sugiyama T
    • Journal Title

      J Diabetes Investigation

      Volume: 11 Issue: 1 Pages: 216-222

    • DOI

      10.1111/jdi.13101

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low birth weight is associated with type 2 diabetes mellitus in Japanese adults: The Toon Health Study.2020

    • Author(s)
      Yokoyama M; Saito I; Ueno M, Maruyama K, Osawa H, Tanigawa T, Sugiyama T.
    • Journal Title

      J Diabetes Investigation

      Volume: 11 Issue: 6 Pages: 1643-1650

    • DOI

      10.1111/jdi.13274

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations between glycosylated hemoglobin level at less than 24 weeks of gestation and adverse pregnancy outcomes in Japan: The Japan Environment and Children’s Study (JECS)2020

    • Author(s)
      Iwama N, Sugiyama T, Metoki H, Saito M, Hoshiai T, Watanabe Z, Tanaka K, Sasaki S, Sakurai K, Ishikuro M, Obara T, Tatsuta N, Nishigori H, Kuriyama S, Arima T, Nakai K, Yaegashi N, and JECS Group
    • Journal Title

      Diabetes Research and Clinical Practice

      Volume: 169 Pages: 108377-108377

    • DOI

      10.1016/j.diabres.2020.108377

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Difference in the prevalence of gestational diabetes mellitus according to gestational age at 75-g oral glucose tolerance test, in Japan: The JAGS trial.2019

    • Author(s)
      Iwama N, Sugiyama T, Metoki H, Kusaka H, Yaegashi N, Sagawa N, Hiramatsu Y, Toyoda N
    • Journal Title

      J Diabetes Investig

      Volume: 印刷中 Issue: 6 Pages: 1576-1585

    • DOI

      10.1111/jdi.13044

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paternal height has an impact on fetal growth in a Japanese population:2019

    • Author(s)
      Takagi K, Iwama N, Metoki H, Matsubara Y, Uchikura Y, Matsubara K, Nishigori H, Saito M, Fujiwara I, Sakurai K, Kuriyama S, Arima T, Nakai K, Yaegashi N, Sugiyama T
    • Journal Title

      Journal of Developmental Origins of Health Disease

      Volume: 11 Issue: 5 Pages: 1-13

    • DOI

      10.1017/s2040174418001162

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 妊娠中の食餌介入が次世代へ及ぼす影響2021

    • Author(s)
      上野愛実、杉山 隆
    • Organizer
      日本女性栄養・代謝学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Pregnancy outcomes of GDM and pre-existing diabetes mellitus in Japan2019

    • Author(s)
      Takashi Sugiyama
    • Organizer
      International Diabetes Federation 2019 in Busan シンポジウム
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Comparison of pregnancy outcomes between women with early-onset and late-onset gestational diabetes2019

    • Author(s)
      Takashi Sugiyama
    • Organizer
      The 10th International Symposium on Diabetes, Hypertension, Metabolic Syndrome and Pregnancy
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] DOHaDの検証:DOHaDのOverviewとUpdate2019

    • Author(s)
      杉山 隆
    • Organizer
      第8回日本DOHaD学会学術集会 シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 産婦人科的視点からみた肥満症2019

    • Author(s)
      杉山 隆
    • Organizer
      第17回日本肥満学会肥満症サマーセミナー
    • Related Report
      2019 Research-status Report

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

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