Systematic understanding of lipids absorption mechanisms based on activity balance between sterol transporters and its application to disease treatment

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H06219
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: YAMANASHI Yoshihide 東京大学, 医学部附属病院, 助教 (20582018)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 脂質トランスポーター / 消化管吸収 / 動脈硬化症 / リポタンパク質

Outline of Final Research Achievements

The purpose of this study is to clarify the regulatory system of dietary lipids absorption based on the activity balance between ABCG5/G8, a cholesterol exporter, and NPC1L1, a cholesterol importer, and to evaluate effects of the system on atherosclerosis progression.
In vitro transport assays using NPC1L1 overexpressing cells and in vivo absorption studies using Npc1l1 knockout mice demonstrated that NPC1L1 is involved in the absorption of various dietary lipids. In addition, in vivo analyses using atherosclerosis mouse models showed the pathophysiological importance of NPC1L1 for the development and progression of atherosclerosis.

Free Research Field

脂質動態学

Academic Significance and Societal Importance of the Research Achievements

本研究により、これまで未解明であったいくつかの食事由来脂質の消化管吸収経路について、コレステロール輸送体が関わることが明らかとなり、生理学的・栄養学的に重要な成果が得られた。また、動脈硬化症の発症・進行に関わりうる新たな因子を見出すことにも成功した。この発見は、将来、動脈硬化性疾患の新たな予防法や治療法の開発ならびに、動脈硬化症発症リスクの新規バイオマーカーの開発にも繋がる可能性を秘めており、基礎のみならず臨床的にも重要な成果が得られた。