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

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04882
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Hamamatsu 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
• Keywords: DOHaD / 妊娠 / 栄養 / 脂肪肝 / NAFLD / 小胞体ストレス / 胎児 / 先制医療

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.

Free Research Field

周産期医学、DOHaD