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Metabolomics reveals risk factors for the development of diseases in low-birth weight infants for preemptive medicine

Research Project

Project/Area Number 18K07829
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionJuntendo University

Principal Investigator

Kaga Naoko  順天堂大学, 大学院医学研究科, 助教 (80338342)

Co-Investigator(Kenkyū-buntansha) 高 ひかり  順天堂大学, 大学院医学研究科, 助教 (60338374)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords胎生期低糖質カロリー制限 / 低出生体重 / メチルドナー補充 / 血中メタボローム解析 / 耐糖能異常 / 血清メタボローム / 質量分析 / 脂質代謝 / 胎生期低栄養 / メチルドナー / DOHaD / 非感染性慢性疾患(NCDs) / 血中代謝物 / NCDs / メタボロミクス / 非感染性慢性疾患
Outline of Final Research Achievements

Undernutrition during fetal period causes low birth weight and risk of developing disease in adulthood. In the blood of infants from low carbohydrate calorie restricted dams, several metabolite levels were changed compare to those from voluntary intake dams. But some of them were recovered to around control level by methyl donor supplementation through their mother at late gestation or lactation period. Among these blood metabolites, the metabolites, which have already been reported as blood biomarkers to predict glucose intolerance and impaired renal function, were detected. These results suggest that early methyl donor supplementation through mother may contribute to improvement at least glucose intolerance, impaired renal function of these low-birth weight infants from low carbohydrate caloric restricted mother.

Academic Significance and Societal Importance of the Research Achievements

発達過程における負の環境因子は、エピジェネティックな変化を誘導し記憶される。本研究では胎生期低糖質カロリー制限による低出生体重仔のDNAメチル化低下に着目し、メチルドナー補充による代謝への影響を解析した。血中代謝産物の解析から、低糖質カロリー制限による低出生体重仔では、胎仔の時点ですでに早期耐糖能異常が予測されたが、妊娠後期・授乳期のメチルドナー補充により改善がみられた。これは、胎生期低糖質カロリー制限により惹起された代謝変動の回復に、メチルドナーが寄与したことを暗示している。即ち適正な時期の的確な介入は、発達期に記憶された次世代まで続く疾患発症リスクの回避を可能にさせることを示唆している。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 2020 2019 2018

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (3 results)

  • [Journal Article] Biochemical characterization of mitochondria from adult worms and plerocercoid larvae of Spirometra mansoni shows mixed populations of anaerobic and aerobic mitochondria2023

    • Author(s)
      Takamiya Shinzaburo、Nakamura Takeshi、Tsubokawa Daigo、Tsuji Naotoshi、Fukuda Koichi、Yamasaki Hiroshi、Fujimura Tsutomu、Taka Hikari、Kaga Naoko、Kobayashi-Tanabe Momoko、Matsuda Motoo、Mita Toshihiro
    • Journal Title

      Parasitology International

      Volume: 92 Pages: 102695-102695

    • DOI

      10.1016/j.parint.2022.102695

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Effect of Long-Term Inorganic Iodine on Intrathyroidal Iodothyronine Content and Gene Expression in Mice with Graves' Hyperthyroidism2023

    • Author(s)
      Uchida Toyoyoshi、Shimamura Mika、Taka Hikari、Kaga Naoko、Miura Yoshiki、Nishida Yuya、Nagayama Yuji、Watada Hirotaka
    • Journal Title

      Thyroid

      Volume: 33 Issue: 3 Pages: 330-337

    • DOI

      10.1089/thy.2022.0496

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Comprehensive Analysis of Plasma Cytokines and Metabolites Shows an Association between Galectin-9 and Changes in Peripheral Lymphocyte Subset Percentages Following Coix Seed Consumption2022

    • Author(s)
      Suzuki Yoshio、Miyahara Taisei、Jinnouchi Minami、Miura Yoshiki、Taka Hikari、Kaga Naoko、Ohara-Takada Akiko
    • Journal Title

      Nutrients

      Volume: 14 Issue: 9 Pages: 1696-1696

    • DOI

      10.3390/nu14091696

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short-term physical inactivity induces diacylglycerol accumulation and insulin resistance in muscle via lipin1 activation2021

    • Author(s)
      Kakehi Saori、Tamura Yoshifumi、Ikeda Shin-ichi、Kaga Naoko、Taka Hikari、Ueno Noriko、Shiuchi Tetsuya、Kubota Atsushi、Sakuraba Keishoku、Kawamori Ryuzo、Watada Hirotaka
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 321 Issue: 6 Pages: E766-E781

    • DOI

      10.1152/ajpendo.00254.2020

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nicotine Oral Administration Attenuates DSS-Induced Colitis Through Upregulation of Indole in the Distal Colon and Rectum in Mice2021

    • Author(s)
      Nakajima Akihito、Shibuya Tomoyoshi、Sasaki Takashi、Lu Yu Jie、Ishikawa Dai、Haga Keiichi、Takahashi Masahito、Kaga Naoko、Osada Taro、Sato Nobuhiro、Nagahara Akihito
    • Journal Title

      Frontiers in Medicine

      Volume: 8

    • DOI

      10.3389/fmed.2021.789037

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alterations of the gut ecological and functional microenvironment in different stages of multiple sclerosis2020

    • Author(s)
      Takewaki D, Suda W, Sato W, Takayasu L, Kumar N, Kimura K, Kaga N, Mizuno T, Miyake S, Hattori M, Yamamura T
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 117 Issue: 36 Pages: 22402-22412

    • DOI

      10.1073/pnas.2011703117

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A metabolic profile of polyamines in parkinson disease: A promising biomarker2019

    • Author(s)
      Saiki Shinji、Sasazawa Yukiko、Fujimaki Motoki、Kamagata Koji、Kaga Naoko、Taka Hikari、Li Yuanzhe、Souma Sanae、Hatano Taku、Imamichi Yoko、Furuya Norihiko、Mori Akio、Oji Yutaka、Ueno Shin‐Ichi、Nojiri Shuko、Miura Yoshiki、Ueno Takashi、Funayama Manabu、Aoki Shigeki、Hattori Nobutaka
    • Journal Title

      Annals of Neurology

      Volume: 86 Issue: 2 Pages: 251-263

    • DOI

      10.1002/ana.25516

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correction: Targeting mantle cell lymphoma metabolism and survival through simultaneous blockade of mTOR and nuclear transporter exportin-12019

    • Author(s)
      Sekihara Kazumasa、Saitoh Kaori、Han Lina、Ciurea Stefan、Yamamoto Shinichi、Kikkawa Mika、Kazuno Saiko、Taka Hikari、Kaga Naoko、Arai Hajime、Miida Takashi、Andreeff Michael、Konopleva Marina、Tabe Yoko
    • Journal Title

      Oncotarget

      Volume: 10 Issue: 63 Pages: 6842-6842

    • DOI

      10.18632/oncotarget.27309

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Choline-related metabolites influenced by feeding patterns in preterm and term infants2018

    • Author(s)
      Shoji Hiromichi、Taka Hikari、Kaga Naoko、Ikeda Naho、Hisata Ken、Miura Yoshiki、Shimizu Toshiaki
    • Journal Title

      The Journal of Maternal-Fetal & Neonatal Medicine

      Volume: ー Issue: 2 Pages: 1-6

    • DOI

      10.1080/14767058.2018.1488165

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of FAO in AML co-cultured with BM adipocytes: mechanisms of survival and chemosensitization to cytarabine.2018

    • Author(s)
      Tabe Y, Saitoh K, Yang H, Sekihara K, Yamatani K, Ruvolo V, Taka H, Kaga N, Kikkawa M, Arai H, Miida T, Andreeff M, Spagnuolo PA, Konopleva M.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 16837-16837

    • DOI

      10.1038/s41598-018-35198-6

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease.2018

    • Author(s)
      Fujimaki M, Saiki S, Li Y, Kaga N, Taka H, Hatano T, Ishikawa KI, Oji Y, Mori A, Okuzumi A, Koinuma T, Ueno SI, Imamichi Y, Ueno T, Miura Y, Funayama M, Hattori N.
    • Journal Title

      Neurology.

      Volume: 90 Issue: 5 Pages: 1-8

    • DOI

      10.1212/wnl.0000000000004888

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 低出生体重倹約型表現型モデルラットの骨格筋と脂肪組織の解析2022

    • Author(s)
      根本 崇宏、加賀 直子、高 ひかり、上野 隆
    • Organizer
      第95回日本生化学大会 2022年11月9日―11日
    • Related Report
      2022 Annual Research Report
  • [Presentation] 出生後母乳を介したメチルドナー補充が低栄養出生仔へ与える影響2019

    • Author(s)
      加賀直子、高ひかり、上野隆、三浦芳樹、根本崇宏
    • Organizer
      第92回 日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 低出生体重仔への高脂肪食負荷による非感染性慢性疾患(NCDs)発症リスクへの影響2018

    • Author(s)
      高ひかり、加賀直子、上野隆、三浦芳樹、根本崇宏
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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