Analyses of physiological functions of lipoproteins focusing on functional lipid contents and evaluation of their effects on lifestyle-related diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19643
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 58:Society medicine, nursing, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Yamanashi Yoshihide 東京大学, 医学部附属病院, 講師 (20582018)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: LDL / 機能性脂質 / 動脈硬化症 / 非アルコール性脂肪肝

Outline of Final Research Achievements

This study focused on functional lipid X, whose lipoprotein distribution pattern shifts dramatically from HDL to LDL in dyslipidemia, and was designed to clarify the physiological activity, target molecules, and pathophysiological significance of LDL-distributed lipid X (LDL-lipidX).
Our studies have revealed that LDL-lipid X has an inflammation-inducing effect as its physiological activity, and we succeeded in identifying candidate target molecules for the activity. We also succeeded in generating and breeding mice deficient in the genes for the target molecules of LDL-lipid X using the CRISPR-Cas9 system, and obtained the mice necessary for analyzing the pathophysiological significance of LDL-lipid X.

Free Research Field

脂質動態学

Academic Significance and Societal Importance of the Research Achievements

本研究により、脂質異常症の進行に伴い増加する機能性脂質Xを含む新規LDLサブタイプが炎症惹起作用を有すること、またその標的作用分子の候補が見出された。今後、本研究で作出した標的分子の遺伝子欠損マウスを用いて、当該LDLサブタイプの病態生理学的意義が明らかになることで、生活習慣病に対する新たなバイオマーカー、予防/治療戦略、創薬標的の提唱に繋がる可能性があり、公衆衛生および健康科学上の大きな貢献が期待される。