Effects of Fructose Consumption on the Central Nervous System of the Next Generation

• Project/Area Number: 18K17987
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Fujita Health University
• Principal Investigator: Yamada Hiroya 藤田医科大学, 医学部, 講師 (80610352)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Discontinued (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: DOHaD / エピジェネティクス / 栄養 / 体質 / DNAメチル化 / 海馬 / フルクトース / 中枢神経

Outline of Final Research Achievements

The aim of this study is to clarify the effects of maternal excessive fructose intake on the hippocampus of offspring.　Specifically, we demonstrated that maternal fructose intake affects the molecular mechanisms involved in hippocampal development and contributes to phenotypic abnormalities.

Academic Significance and Societal Importance of the Research Achievements

「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示唆されている。本研究はフルクトースの過剰摂取が、次世代に及ぼす影響を明らかにするものであり、現代社会におけるフルクトース過剰摂取の悪影響をDOHaD説により証明するものである。

Research Products

• [Journal Article] Maternal fructose-induced oxidative stress occurs via Tfam and Ucp5 epigenetic regulation in offspring hippocampi. (2019)
  • Author(s): Yamada H, Munetsuna E, Yamazaki M, Mizuno G, Sadamoto N, Ando Y, Fujii R, Shiogama K, Ishikawa H, Suzuki K, Shimono Y, Ohashi K, Hashimoto S
  • Journal Title: FASEB journao Volume: 33 Issue: 10 Pages: 11431-11442
  • DOI: 10.1096/fj.201901072r
  • Peer Reviewed
• [Journal Article] Maternal high-fructose intake increases circulating corticosterone levels via decreased adrenal corticosterone clearance in adult offspring. (2019)
  • Author(s): Munetsuna E, Yamada H, Yamazaki M, Ando Y, Mizuno G, Hattori Y, Sadamoto N, Ishikawa H, Ohta Y, Fujii R, Suzuki K, Hashimoto S, Ohashi K
  • Journal Title: Journal of nutritional biochemistry Volume: 67 Pages: 44-50
  • DOI: 10.1016/j.jnutbio.2019.01.016
  • Peer Reviewed
• [Journal Article] Maternal fructose intake disturbs ovarian estradiol synthesis in rats (2018)
  • Author(s): Munetsuna E, Yamada H, Yamazaki M, Ando Y, Mizuno G, Ota T, Hattori Y, Sadamoto N, Suzuki K, Ishikawa H, Hashimoto S, Ohashi K.
  • Journal Title: Life Sciences Volume: 印刷中 Pages: 1231-1239
  • DOI: 10.1016/j.lfs.2018.04.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter. (2018)
  • Author(s): Yamazaki M, Yamada H, Munetsuna E, Ishikawa H, Mizuno G, Mukuda T, Mouri A, Nabeshima T, Saito K, Suzuki K, Hashimoto S, Ohashi K.
  • Journal Title: FASEB J. Volume: 32 Issue: 5 Pages: 2549-2562
  • DOI: 10.1096/fj.201700783rr
  • Peer Reviewed / Open Access
• [Presentation] Maternal fructose consumption during gestation and lactation downregulated Igf-1 expression in offspring rat. (2019)
  • Author(s): Yamada Hiroya.
  • Organizer: 11th DOHaD World Congress
  • Int'l Joint Research
• [Presentation] 母獣のフルクトース過剰摂取が仔海馬Uncoupling Proteins発現に与える影響 (2018)
  • Author(s): 貞本奈緒、山田宏哉山崎未来、山田宏哉、宗綱栄二、服部裕次、下平大輝、
  • Organizer: 日本DOHaDg学会
• [Presentation] 母獣のフルクトース過剰摂取は生後のストレス感受性を亢進する (2018)
  • Author(s): 山崎未来、山田宏哉、宗綱栄二、貞本奈緒、服部裕次、下平大輝、
  • Organizer: 日本DOHaD学会
• [Presentation] 妊娠授乳期の母体フルクトース過剰摂取が仔に及ぼす影響 (2018)
  • Author(s): 服部裕次、村瀬悠理、山田宏哉、宗綱栄二、山崎未来、貞本奈緒、安藤嘉崇、石川浩章、鈴木康司、大橋紘二
  • Organizer: 日本栄養食糧学会