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Developmental Origins of Hepatic Steatosis; A Possible Involvement of Endoplasmic Reticulum Stress Response

Research Project

Project/Area Number 15H04882
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Ito Hiroaki  浜松医科大学, 医学部附属病院, 教授 (70263085)

Co-Investigator(Kenkyū-buntansha) 谷口 千津子  浜松医科大学, 医学部附属病院, 特任助教 (20397425)
鈴木 一有  浜松医科大学, 医学部附属病院, 講師 (50456571)
Co-Investigator(Renkei-kenkyūsha) MIYAMOTO Yoshihiro  独立行政法人国立循環器病研究センター, 予防検診部/研究開発基盤センター予防医学・疫学情報部, 部長 (10312224)
OGAWA Yoshihiro  東京医科歯科大学, 難治疾患研究所, 教授 (70291424)
TUCHIYA Kenji  浜松医科大学, 子どものこころの発達研究センター, 特任教授 (20362189)
MASUZAKI Hiroaki  現琉球大学, 医学部, 教授 (00291899)
UDAGAWA Jun  現滋賀医科大学, 医学部, 教授 (10284027)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
KeywordsDOHaD / 妊娠 / 栄養 / 脂肪肝 / NAFLD / 小胞体ストレス / 胎児 / 先制医療 / 肝脂肪変性 / 低栄養 / 生活習慣病 / 低出生体重児 / 胎児発育不全 / 肥満 / 胎生期低栄養 / 成人病 / メタボリックシンドローム
Outline of Final Research Achievements

We developed a mice animal model of undernourishment in utero deteriorating hepatic steatosis in adult period. Using this animal model, we demonstrated that undernourishment in utero programs the augmentation of endoplasmic reticulum stress in the lever in response to obesogenic diet in adult period, causatively associated with the deterioration of hepatic steatosis and choronic inflammation. The alleviation of ER stress with the treatment of chemical chaperone, tauroursodeoxycholic acid (TUDCA), markedly improved both hepatic steatosis and chronic inflammation. The alleviation of ER stress would be a promising strategy of preemptive medicine against developmental origins of hepatic steatosis.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (42 results)

All 2018 2017 2016 2015

All Journal Article (19 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 19 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 1 results,  Invited: 14 results) Book (2 results)

  • [Journal Article] Placental pathology predicts infantile physical development during first 18 months in Japanese population: Hamamatsu birth cohort for mothers and children (HBC Study)2018

    • Author(s)
      Yaguchi Chizuko、Itoh Hiroaki、Tsuchiya Kenji J.、Furuta-Isomura Naomi、Horikoshi Yoshimasa、Matsumoto Masako、Jeenat Ferdous U.、Keiko Muramatsu-Kato、Kohmura-Kobatashi Yukiko、Tamura Naoaki、Sugihara Kazuhiro、Kanayama Naohiro
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 4 Pages: e0194988-e0194988

    • DOI

      10.1371/journal.pone.0194988

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of placental weight and fetal/placental weight ratio Z score on fetal growth and the perinatal outcome2018

    • Author(s)
      Matsuda Yoshio、Itoh Toshiya、Itoh Hiroaki、Ogawa Masaki、Sasaki Kemal、Kanayama Naohiro、Matsubara Shigeki
    • Journal Title

      International Journal of Medical Sciences

      Volume: 15 Issue: 5 Pages: 484-491

    • DOI

      10.7150/ijms.23107

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The correlation of morphological and thrombotic villous arterial lesions with fetal Doppler echocardiographic measurements in the placentas of low-risk term pregnancies2018

    • Author(s)
      Sekii Katsuyuki、Yaguchi Chizuko、Itoh Hiroaki
    • Journal Title

      European Journal of Obstetrics & Gynecology and Reproductive Biology

      Volume: 223 Pages: 39-45

    • DOI

      10.1016/j.ejogrb.2018.02.006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue oxygen saturation levels from fetus to neonate.2017

    • Author(s)
      Mukai M, Uchida T, Itoh H, Suzuki H, Niwayama M, Kanayama N
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 印刷中 Issue: 5 Pages: 1-4

    • DOI

      10.1111/jog.13295

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reproductive technologies and the risk of congenital heart defects2017

    • Author(s)
      Iwashima Satoru、Ishikawa Takamichi、Itoh Hiroaki
    • Journal Title

      Human Fertility

      Volume: 20 Issue: 1 Pages: 14-21

    • DOI

      10.1080/14647273.2016.1254352

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of antenatal antithrombin activity with perinatal liver dysfunction: prospective multicenter study2017

    • Author(s)
      Morikawa M, Suzuki H, Obata-Yasuda M, Kassai M, Itoh H, Ohkuchi A, Hamada H, Aoki S, Kanayama N, Minakami N.
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 印刷中 Issue: 7 Pages: 1378-1386

    • DOI

      10.1111/jgh.13714

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its relationship with their maternal background and neonatal health2017

    • Author(s)
      Harauchi Satoe、Osawa Takashi、Kubono Naoko、Itoh Hiroaki、Naito Takafumi、Kawakami Junichi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 23 Issue: 7 Pages: 446-451

    • DOI

      10.1016/j.jiac.2017.03.015

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amniotic fluid embolism: Pathophysiology from the perspective of pathology.2017

    • Author(s)
      Tamura N, Farhana M, Oda T, Itoh H, Kanayama N.
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 印刷中 Issue: 4 Pages: 627-632

    • DOI

      10.1111/jog.13284

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Annual Report of the Perinatology Committee, Japan Society of Obstetrics and Gynecology 2015: Proposal of urgent measures to reduce maternal deaths.2017

    • Author(s)
      Takeda S, Takeda J, Murakami K, Kubo T, Hamada H, Murakami M, Makino S, Itoh H, Ohba T, Naruse K, Tanaka H, Kanayama N, Matsubara S, Sameshima H, Ikeda T.
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 43 Issue: 1 Pages: 5-7

    • DOI

      10.1111/jog.13184

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its relationship with their maternal background and neonatal health2017

    • Author(s)
      Harauchi S, Osawa T, Kubono N, Itoh H, Naito T, Kawakami J.
    • Journal Title

      J Infect Chemother

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leiomyomatosis peritonealis disseminata with aromatase cytochrome P450 expression in a postmenopausal woman: a case study with literature review.2017

    • Author(s)
      Matsuya OM, Sugihara K, Yaguchi C, Itoh H, Kitamura H, Naohiro Kanayama N, Arahori K.
    • Journal Title

      Eur J Gynaecol Oncol

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maternal postpartum depressive symptoms predict delay in non-verbal communication in 14-month-old infants.2016

    • Author(s)
      Kawai E, Takagai S, Takei N, Itoh H, Kanayama N, Tsuchiya JK, for HBC Study Team.
    • Journal Title

      Infant Behav Dev

      Volume: 46 Pages: 33-35

    • DOI

      10.1016/j.infbeh.2016.11.006

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Undernourishment in utero and hepatic steatosis in later life; A potential issue in Japanese people: A Review.2016

    • Author(s)
      Itoh H, Muramatsu-Kato K, Ferdous UJ, Kohmura-Kobayashi Y, Naohiro Kanayama N.
    • Journal Title

      Congenit Anom

      Volume: - Issue: 6 Pages: 1-2

    • DOI

      10.1111/cga.12200

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Randomized double-blind comparison of the effects of intramyometrial and intravenous oxytocin during elective cesarean section.2016

    • Author(s)
      Akinaga C, Uchizaki S, Kurita T, Taniguchi M, Makino H, Suzuki A, Uchida T, Suzuki K, Itoh H, Tani S, Sato S, Terui K.
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 42 Issue: 4 Pages: 404-409

    • DOI

      10.1111/jog.12926

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fetal Environment and Glycosylation Status in Neonatal Cord Blood: A Comprehensive Mass Spectrometry-based Glycosylation Analysis.2016

    • Author(s)
      Sato R, Tsuchiya KJ, Matsuzaki H, Takei N, Itoh H, Kanayama N, Suda T, Watanabe H, Ohashi T, Tanaka M, Nishimura S, Maekawa M, HBC study group
    • Journal Title

      Medicine (Baltimore).

      Volume: 95(14) Issue: 14 Pages: e3219-e3219

    • DOI

      10.1097/md.0000000000003219

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison between enoxaparin sodium and unfractionated heparin administered within 24 hours of cesarean section2016

    • Author(s)
      Mukai M, Kashiwagi Y, Itoh H, Furuta N, Murakami H, Tamura N, Uchida T, Suzuki K, Sugimura M, Kanayama N.
    • Journal Title

      Hypertension Research in Pregnancy

      Volume: 4 Issue: 1 Pages: 16-23

    • DOI

      10.14390/jsshp.HRP2015-010

    • NAID

      130005250044

    • ISSN
      2187-5987, 2187-9931
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Undernourishment in utero Primes Hepatic Steatosis in Adult Mice Offspring on an Obesogenic Diet; Involvement of Endoplasmic Reticulum Stress2015

    • Author(s)
      Muramatsu-Kato K, Itoh H, Kohmura-Kobayashi Y, Ferdous UJ, Tamura N, Yaguchi C, Uchida T, Suzuki K, Hashimoto K, Suganami T, Ogawa Y, Kanayama N
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 16867-16867

    • DOI

      10.1038/srep16867

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Morphological characteristics of the placental basal plate in IVF pregnancies: a possible association with the amount of bleeding in delivery2015

    • Author(s)
      Yuki Nakamura,Chizuko yaguchi,Hiroaki Itoh Ryoko Sakamoto,Takako Kimura,Naomi Furuta,Toshiyuki Uchida,Naoaki Tamura,Kazunao Suzuki,Kazuhiro Sumimoto,Yumiko Matsuda,Toshiki Matsura,Mitsura Nishimura,Naohiro Kanayama
    • Journal Title

      Human Pathology

      Volume: inprint Issue: 8 Pages: 1171-1179

    • DOI

      10.1016/j.humpath.2015.04.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Measurement of maternal cerebral tissue hemoglobin levels by Near-infrared time-resolved spectroscopy (TRS) in the peripartum period.2015

    • Author(s)
      Suzuki K, Itoh H, Mukai M, Yamazaki K, Uchida T, Maeda H, Oda M, Yamaki E, Suzuki H, Kanayama N
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 41 Issue: 6 Pages: 876-883

    • DOI

      10.1111/jog.12639

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 妊婦のエネルギー摂取不足が成長後の児の脂肪肝発症リスクに及ぼす影響の解析:エピゲノムの変容からのアプローチ2018

    • Author(s)
      伊東宏晃
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Undernourishment in utero as well as endoplasmic reticulum stress alleviation affects lipid profile of the mice fatty liver2017

    • Author(s)
      Hiroaki Itoh
    • Organizer
      10th World Congress on Developmental Origins of Health and Disease (DOHaD)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Undernorishment in utero and hepatic steatosis in later life; a poosible involvement of endoplasmic reticulum stress2017

    • Author(s)
      伊東宏晃
    • Organizer
      第94回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 妊婦のエネルギー摂取不足と成長後の児の脂肪肝発症リスクの関わり2017

    • Author(s)
      伊東宏晃
    • Organizer
      第6回日本DOHaD学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 胎生期の低栄養が小胞体ストレス応答を介して成長後の児の脂肪肝発症リスク形成 に関与する可能性について2016

    • Author(s)
      村松慧子、伊東宏晃他
    • Organizer
      第68回日本産科婦人科学会学術講演会
    • Place of Presentation
      東京
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胎生期の低栄養と成長後の児の脂肪肝発症リスク形成の関係-小胞体ストレスの関与-2016

    • Author(s)
      村松慧子、伊東宏晃他
    • Organizer
      第52回日本周産期・新生児医学会学術集会
    • Place of Presentation
      富山
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胎生期低栄養はマウス産生仔の肝細胞腫大と肝細胞内の脂肪蓄積量の両者の増加を促す2016

    • Author(s)
      Urmi Jeenat Ferdous, 伊東宏晃他
    • Organizer
      第52回日本周産期・新生児医学会学術集会
    • Place of Presentation
      富山
    • Related Report
      2016 Annual Research Report
  • [Presentation] 妊婦のエネルギー摂取不足と成長後の児の脂肪肝発症リスク2016

    • Author(s)
      伊東宏晃
    • Organizer
      第86回日本衛生学会学術総会
    • Place of Presentation
      旭川
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 妊婦のエネルギー摂取不足が成長後の児の脂肪肝発症リスクに及ぼす影響の解析2016

    • Author(s)
      伊東宏晃
    • Organizer
      第119回日本小児科学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 会長特別企画  「先制医療:DOHaD学説の視点から」2016

    • Author(s)
      伊東宏晃
    • Organizer
      第59回糖尿病学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 「ニュージーランド、日本2国間のDOHaD研究協力の取り組みーオークランド大学Liggins研究所と連携する重要性ー」2016

    • Author(s)
      伊東宏晃
    • Organizer
      第5回日本DOHaD研究会学術集会
    • Place of Presentation
      東京
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Undernourishment in utero and Hepatic Steatosis in Later Life; A Possible Involvement of Endoplasmic Reticulum Stress2016

    • Author(s)
      伊東宏晃
    • Organizer
      第56回日本先天異常学会学術集会
    • Place of Presentation
      姫路
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 妊婦の栄養摂取と次世代の健康2016

    • Author(s)
      伊東宏晃
    • Organizer
      第29回静岡県母性衛生学会学術集会
    • Place of Presentation
      静岡
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 産科医から管理栄養士、栄養士の皆様へお伝えしたいこと2016

    • Author(s)
      伊東宏晃
    • Organizer
      第63回日本栄養改善学会学術集会
    • Place of Presentation
      青森
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] SGAとメタボリックシンドローム発症リスク ー胎生期低栄養マウスモデルの検討からー2016

    • Author(s)
      伊東宏晃
    • Organizer
      第27回日本日本成長学会学術集会
    • Place of Presentation
      米子
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 胎生期の環境とepigenetics ーDOHaD学説の視点からー2016

    • Author(s)
      伊東宏晃
    • Organizer
      第2回日本産科婦人科遺伝診療学会
    • Place of Presentation
      京都
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 教育講演 「妊婦のエネルギー摂取不足と脂肪肝発症リスク」2015

    • Author(s)
      伊東宏晃
    • Organizer
      Pfizer Endocrinology Forum 2015
    • Place of Presentation
      東京
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 黒ネズミと戯れて16年 ―胎生期低栄養マウスモデルの開発から見果てぬ夢を追い求めて―2015

    • Author(s)
      伊東宏晃
    • Organizer
      第3回 新生児指導医教育セミナー
    • Place of Presentation
      仙台
    • Year and Date
      2015-08-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] シンポジウム: DOHaDの科学的基盤確立シンポジウム 「産科の視点よりDOHaDに学ぶこととその限界」2015

    • Author(s)
      伊東宏晃
    • Organizer
      第4回日本DOHaD研究会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2015-08-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] シンポジウム:子宮内膜環境と将来のメタボリック症候群-DOHaDの観点から 「妊婦のエネルギー摂取不足と児が将来脂肪肝を発症するリスクの関わりについて」2015

    • Author(s)
      伊東宏晃
    • Organizer
      第88回日本内分泌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ミニワークショップ:胎生期低栄養環境に引き続く出生後の著しいcatch-up growthが成長後のメタボリックシンドロームの発症リスクに及ぼす影響 : 小胞体ストレスとの関わり2015

    • Author(s)
      幸村有季子、村松慧子、山崎かおり、伊熊ことみ、向麻利、古田直美、田村直晃、内田季之、鈴木一有、杉原一廣、伊東宏晃、金山尚裕
    • Organizer
      第67回日本周産期新生児学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2015-04-11
    • Related Report
      2015 Annual Research Report
  • [Book] Precision Medicine in GYnecology and Obstetrics2017

    • Author(s)
      (分担執筆)Itoh H and Kanayama N
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] DOHaD; From Biological Basis to Clinical Significance2017

    • Author(s)
      (分担執筆)Itoh H and Kanayama N
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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