Prevention research of Nonalcoholic Fatty Liver Disease due to Intrauterine growth restriction Using Bile Acid Reabsorption Inhibitors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17343
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Juntendo University
• Principal Investigator: Nakano Satoshi 順天堂大学, 医学部, 非常勤助教 (70826453)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 子宮内発育遅延 / 低出生体重児 / 低栄養 / 非アルコール性脂肪性肝疾患 / 胆汁酸再吸収阻害薬

Outline of Final Research Achievements

To create a model of intrauterine growth retardation, uterine artery ligation was attempted on the 18th day of pregnancy in rats, but no significant weight loss was obtained compared to the Control group. Next, the experimental animals were changed from rats to mice to try to create a model of intrauterine growth retardation due to protein-restricted dietary stress during pregnancy. Initially, the evaluation of the birth pups did not proceed due to postnatal failure and predation caused by stress from the protein-restricted mother, but stable development of the pups was achieved by adjusting the growth environment. Although the intrauterine growth retardation model mothers' offspring did not differ significantly, their birth weight was lower and Cyp7a1 expression in the liver was also reduced compared to the Control group.

Free Research Field

小児栄養消化器病学

Academic Significance and Societal Importance of the Research Achievements

本邦では、出生数が減少傾向にあるにも関わらず、全出生児に占める低出生体重児の割合は年々増加し、10%前後を占める。LBWIの主要な原因の一つに子宮内発育遅延がある。近年、IUGRによるLBWIが、将来の非アルコール性脂肪性肝疾患、2型糖尿病、慢性腎臓病などの疾患リスクを上げることが判明した。食生活の欧米化と飽食の影響で、非アルコール性脂肪性肝疾患は増加しており、特に小児期・思春期の増加が顕著である。以上の背景から、申請者は、IUGR児のNAFLD発症を未然に防ぐことが重要と考え、本研究の課題とした。