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Effects of Excessive Fructose Consumption on the Next Generation: Investigating Tissue Stem Cells and the DOHaD Hypothesis

Research Project

Project/Area Number 20H04134
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionFujita Health University

Principal Investigator

Yamada Hiroya  藤田医科大学, 医学部, 准教授 (80610352)

Co-Investigator(Kenkyū-buntansha) 宗綱 栄二  藤田医科大学, 医学部, 助教 (30600431)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2022: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsDOHaD / 幹細胞 / エピゲノム / 前駆細胞 / Stem cell / DNAメチル化 / フルクトース / エピジェネティクス / 栄養 / 次世代 / オルガノイド / 未分化細胞 / 胎児 / メタボリックメモリー
Outline of Research at the Start

「健康や疾患の素因は胎児期における栄養状態によって形成される」という新しい概念であるDOHaD(Developmental Origin of Health & Disease)説が提唱され、妊娠期の栄養状態が世代を超え、その子どもの将来にも大きく影響を及ぼすことが注目されている。
本研究は組織幹細胞に焦点を当てた新しいアプローチにより、次世代への悪影響を解き明かすことを目的とする。

Outline of Final Research Achievements

The DOHaD (Developmental Origin of Health & Disease) hypothesis, a novel concept, proposes that the predisposition to health or disease is shaped by the nutritional status during the fetal period. This hypothesis has garnered significant attention, emphasizing that the fetal environment can have profound effects across generations, influencing the future health of the offspring.

Our research has focused on fructose, a natural sweetener commonly consumed in everyday life, within the context of DOHaD studies. This study employs an entirely new approach by concentrating on stem cells to elucidate the adverse effects of fructose on the next generation. By considering our findings on the previously overlooked properties and differentiation abnormalities of tissue stem cells, we anticipate substantial advancements in the understanding of the DOHaD hypothesis.

Academic Significance and Societal Importance of the Research Achievements

近年のフルクトースの爆発的な消費量増加や疫学的な研究を鑑みると、次世代へ負の影響が強く示唆されている。しかしながら、メカニズムに関しては全く不明であるため、社会に警鐘を鳴らすには至っていない。本研究はこれまで制限の無かった妊婦のフルクトース摂取に関して一石を投じることが期待される。
本研究で得られた知見により、疾患形成のメカニズムを理解することができる。疾患リスクの形成を阻止する予防医学につながるばかりでなく、肥満や生活習慣病に耐性を持つ体質獲得につながるため新たな方法の開発につながる。

Report

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

    (19 results)

All 2024 2023 2022 2021 2020

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 4 results) Presentation (8 results)

  • [Journal Article] Impact of maternal fructose intake on liver stem/progenitor cells in offspring: Insights into developmental origins of health and disease2024

    • Author(s)
      Ando Yoshitaka、Munetsuna Eiji、Yamada Hiroya、Ikeya Miyuki、Teshigawara Atsushi、Kageyama Itsuki、Nouchi Yuki、Wakasugi Takuya、Yamazaki Mirai、Mizuno Genki、Tsuboi Yoshiki、Ishikawa Hiroaki、Ohgami Nobutaka、Suzuki Koji、Ohashi Koji
    • Journal Title

      Life Sciences

      Volume: 336 Pages: 122315-122315

    • DOI

      10.1016/j.lfs.2023.122315

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction between Prenatal and Postnatal Exposure to High-Fructose Corn Syrup Increases Gene Expression of <i>Tnfa</i> in Hippocampus of Offspring2023

    • Author(s)
      Yamazaki M, Yamada H, Munetsuna E, Ando Y, Kageyama I, Sadamoto N, Nouchi Y, Teshigawara A, Mizuno G, Ishikawa H, Suzuki K, Hashimoto S, Ohashi K.
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 69 Issue: 4 Pages: 237-242

    • DOI

      10.3177/jnsv.69.237

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2023-08-31
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Maternal High-Fructose Corn Syrup Intake Impairs Corticosterone Clearance by Reducing Renal 11β-Hsd2 Activity via miR-27a-Mediated Mechanism in Rat Offspring2023

    • Author(s)
      Nouchi Y, Munetsuna E, Yamada H, Yamazaki M, Ando Y, Mizuno G, Ikeya M, Kageyama I, Wakasugi T, Teshigawara A, Hattori Y, Tsuboi Y, Ishikawa H, Suzuki K, Ohashi K.
    • Journal Title

      Nutrients

      Volume: 15 Issue: 9 Pages: 2122-2122

    • DOI

      10.3390/nu15092122

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-fructose corn syrup intake increases hepatic mitochondrial DNA copy number and methylation in adolescent rats2023

    • Author(s)
      Mizuno Genki、Yamada Hiroya、Munetsuna Eiji、Ando Yoshitaka、Teshigawara Atsushi、Ito Manaka、Kageyama Itsuki、Nouchi Yuki、Wakasugi Takuya、Sakakibara Tomohide、Yamazaki Mirai、Ishikawa Hiroaki、Suzuki Koji、Hashimoto Shuji、Ohashi Koji
    • Journal Title

      Nutrition Research

      Volume: 110 Pages: 57-65

    • DOI

      10.1016/j.nutres.2022.12.010

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of High-Fructose Corn Syrup Intake on Glucocorticoid Metabolism in Rats During Childhood, Adolescence and Adulthood2022

    • Author(s)
      Nouchi Yuki、Munetsuna Eiji、Yamada Hiroya、Yamazaki Mirai、Ando Yoshitaka、Mizuno Genki、Fujii Ryosuke、Kageyama Itsuki、Wakasugi Takuya、Sakakibara Tomohide、Teshigawara Atsushi、Ishikawa Hiroaki、Shimono Yohei、Suzuki Koji、Hashimoto Shuji、Ohashi Koji
    • Journal Title

      Experimental and Clinical Endocrinology &amp; Diabetes

      Volume: 130 Issue: 12 Pages: 814-820

    • DOI

      10.1055/a-1936-3310

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence2022

    • Author(s)
      Kageyama Itsuki、Yamada Hiroya、Munetsuna Eiji、Yamazaki Mirai、Ando Yoshitaka、Mizuno Genki、Fujii Ryosuke、Nouchi Yuki、Wakasugi Takuya、Sakakibara Tomohide、Teshigawara Atsushi、Ishikawa Hiroaki、Shimono Yohei、Suzuki Koji、Hashimoto Shuji、Ohashi Koji
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 6 Pages: e0270144-e0270144

    • DOI

      10.1371/journal.pone.0270144

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-fructose corn syrup intake has stronger effects on the transcription level of hepatic lipid metabolism-related genes, via DNA methylation modification, in childhood and adolescence than in other generations2022

    • Author(s)
      Mizuno Genki、Yamada Hiroya、Munetsuna Eiji、Ando Yoshitaka、Teshigawara Atsushi、Ito Manaka、Kageyama Itsuki、Nouchi Yuki、Wakasugi Takuya、Sakakibara Tomohide、Yamazaki Mirai、Fujii Ryosuke、Ishikawa Hiroaki、Suzuki Koji、Hashimoto Shuji、Ohashi Koji
    • Journal Title

      Life Sciences

      Volume: 301 Pages: 120638-120638

    • DOI

      10.1016/j.lfs.2022.120638

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal high-fructose corn syrup consumption causes insulin resistance and hyperlipidemia in offspring via DNA methylation of the Pparα promoter region2022

    • Author(s)
      Ando Y, Yamada H, Munetsuna E, Yamazaki M, Kageyama I, Teshigawara A, Nouchi Y, Fujii R, Mizuno G, Sadamoto N, Ishikawa H, Suzuki K, Hashimoto S, Ohashi K.
    • Journal Title

      J Nutr Biochem.

      Volume: . Pages: 108951-108951

    • DOI

      10.1016/j.jnutbio.2022.108951

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maternal fructose intake predisposes rat offspring to metabolic disorders via abnormal hepatic programming2021

    • Author(s)
      Munetsuna E, Yamada H, Yamazaki M, Ando Y, Mizuno G, Hattori Y, Kageyama I, Teshigawara A, Nouchi Y, Ishikawa H, Fujii R, Ohta Y, Suzuki K, Shimono Y, Ohashi K, Hashimoto S.
    • Journal Title

      FASEB J.

      Volume: . Issue: 12

    • DOI

      10.1096/fj.202101276r

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maternal fructose consumption downregulates hippocampal catalase expression via DNA methylation in rat offspring2021

    • Author(s)
      Mizuno G, Munetsuna E, Yamada H, Yamazaki M, Ando Y, Hattori Y, Kageyama I, Teshigawara A, Nouchi Y, Fujii R, Ishikawa H, Suzuki K, Hashimoto S, Ohashi K, Shimono Y.
    • Journal Title

      Nutr Res.

      Volume: 92 Pages: 40-48

    • DOI

      10.1016/j.nutres.2021.06.002

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation.2020

    • Author(s)
      Yamazaki M, Munetsuna E, Yamada H, Ando Y, Mizuno G, Fujii R, Nouchi Y, Kageyama I, Teshigawara A, Ishikawa H, Suzuki K, Shimono Y, Hashimoto S, Ohashi K.
    • Journal Title

      J Nutr Biochem

      Volume: 14 Pages: 108386-108386

    • DOI

      10.1016/j.jnutbio.2020.108386

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] フルクトース過剰摂取モデルラットの肝オルガノイド作成と評価2023

    • Author(s)
      市川 勇斗、山田 宏哉、宗綱 栄二、安藤 嘉崇、景山 斎、野内 佑起、池谷 美幸、波田 薫平、山崎 未来、水野 元貴、 石川 浩章、鈴木 康司、大橋 鉱二
    • Organizer
      第93回日本衛生学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 妊娠前のメチル水銀が次世代の中枢神経系に与える影響2023

    • Author(s)
      伊藤愛佳、山田 宏哉、宗綱 栄二、安藤 嘉崇、若杉 拓哉、景山 斎、大城 雅貴、波田 薫平、山崎 未来、水野 元貴、石川 浩章、鈴木 康司、大橋 鉱二
    • Organizer
      第93回日本衛生学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 妊娠期のフルクトース過剰摂取が胎仔の海馬神経幹細胞に及ぼす影響2022

    • Author(s)
      景山 斎、山田 宏哉、宗綱 栄二、大城 雅貴 、若杉 拓哉、伊藤 愛佳、 野内 佑起 、安藤 嘉崇、山崎 未来、水野 元貴 、石川 浩章、鈴木 康司 、大橋 鉱二
    • Organizer
      第9回日本DOHaD学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 妊娠授乳期のHigh Fructose Corn Syrup過剰摂取が次世代の肝前駆細胞に及ぼす影響2022

    • Author(s)
      池谷 美幸, 山田 宏哉, 宗綱 栄二, 勅使川原 篤志, 安藤 嘉崇, 景山 斎, 野内 佑起, 市川 勇斗, 山崎 未来, 水野 元貴, 石川 浩章, 鈴木 康司, 大橋 鉱二
    • Organizer
      第9回日本DOHaD学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 成長期および成人期のフルクトース過剰摂取が海馬神経栄養因子の発現に及ぼす影響.2021

    • Author(s)
      景山 斎, 宗綱栄二, 山田宏哉, 山崎未来, 安藤嘉崇, 水野元貴, 野内佑起, 勅使川原篤志, 若杉拓哉, 榊原知秀, 石川浩章, 鈴木康司, 大橋鉱二.
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 濃度メチル水銀がラット胎仔神経幹細胞の分化能に及ぼす影響.2021

    • Author(s)
      若杉拓哉, 宗綱栄二, 山田宏哉, 山崎未来, 安藤嘉崇, 水野元貴, 景山 斎, 野内佑起, 勅使川原篤志, 榊原知秀, 石川浩章, 大橋鉱二.
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 妊娠・授乳期のHFCS過剰摂取が次世代のコルチコステロンの分解経路に及ぼす影響の解析.2021

    • Author(s)
      野内佑起, 宗綱栄二, 山田宏哉, 安藤嘉崇, 山崎未来, 水野元貴, 景山 斎, 勅使川原篤志, 榊原知秀, 若杉拓哉, 石川浩章, 鈴木康司, 大橋鉱二.
    • Organizer
      第10回日本DOHaD学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 末梢血におけるHypoxia inducible factor 3A 遺伝子の DNA メチル化率と 脂質異常症 との関連.2021

    • Author(s)
      水野元貴, 山田宏哉, 宗綱栄二, 山崎未来, 安藤嘉崇, 藤井 亮輔, 坪井良樹, 石川浩章, 大橋鉱二, 鈴木康司.
    • Organizer
      第68回日本臨床検査医学会学術集会
    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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