2023 Fiscal Year Final Research Report
Understanding the biological defense system by absorption/excretion balance of dietary lipids and its application to disease treatment
| Project/Area Number |
20H04100
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
徳田 慶太 順天堂大学, 健康データサイエンス学部, 講師 (50762176)
豊田 優 東京大学, 医学部附属病院, 届出研究員 (80650340)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 脂質トランスポーター / 消化管吸収 / 胆汁排泄 / 非アルコール性脂肪性肝疾患 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
The purpose of this study was to clarify the absorption/excretion balance of dietary lipids due to differences in the activities of NPC1L1, a cholesterol importer, and ABCG5/G8, a cholesterol exporter, and the pathophysiological significance of the regulation of this balance in the onset and/or progression of NAFLD. In vitro uptake assays using NPC1L1-overexpressing cells and in vivo experiments using NPC1L1 gene-modified mice have revealed that NPC1L1 is involved in the intestinal absorption and biliary reabsorption of various kinds of oxysterols. In addition, specific oxysterols regulated by NPC1L1 were found to affect the progression of NAFLD.
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| Free Research Field |
脂質動態学
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| 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および胆汁排泄経路について、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、NAFLDの発症・進行に関わりうる新たな脂質を見出すことにも成功した。この発見は、将来、NAFLDの新たな予防法や治療法の開発ならびに、NAFLDの発症・進行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。
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