Hypertriglyceridemia in pregnancy: mouse model and in vivo molecular mechanisms

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16364
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tanaka Masaki 東京大学, 医学部附属病院, 特任臨床医 (80876186)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 高中性脂肪血症 / 妊娠合併症 / apoA-V / 治療法開発 / 動物モデル

Outline of Final Research Achievements

Severe hypertriglyceridemia (HTG) during pregnancy results in life-threatening complications such as severe pancreatitis and fetal death. Hypertriglyceridemic pancreatitis is the leading cause of pancreatitis in pregnancy, but there is currently no established treatment. HTG is exacerbated by secondary factors in addition to genetic predispositions. In this study, we demonstrated that apoA-V-deficient mice are useful as a mouse model of severe HTG in human pregnancy. We also found that apoA-V;SREBP-1c deficient mice have reduced TG elevation during pregnancy and identified several candidate genes that may explain this rescue by gene expression analysis. These findings led us to search for therapeutic modalities using our mouse model.

Free Research Field

脂質異常症

Academic Significance and Societal Importance of the Research Achievements

妊娠時の重度高中性脂肪（TG）血症は重症膵炎・胎児死亡などの重篤な合併症を生じる。高TG血症性膵炎は妊娠中の膵炎の原因の第一位であるが、現時点で確立した治療法はない。その一因として適切なマウスモデルがこれまで存在しなかったことが挙げられる。我々は本研究によりapoA-V欠損マウスはヒト妊娠時高TG血症モデルマウスとして有用であることを示した。また確立したマウスモデルをもとに妊娠時高TG血症の治療を検討した。重篤かつ難治性疾患の治療法開発に貢献した研究であったと考える。