脂質の介する代謝異常による網膜変性機構の解明

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Author: 長田, 秀斗

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Publication date: 2020

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Note (General)：: type:text代謝制御に寄与するアディポネクチン１型受容体(Adipor1)は機能阻害によって網膜色素変性症を呈することが知られているため、Adipor1ノックアウトマウスの網膜および血清を用いてリピドミクス解析を行った。網膜では視細胞外節の形成に重要なDHAを含む脂質の著しい低下を認めた。一方...

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科研費研究者番号 : 50748770

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Material Type: 文書・図像類
Title: 脂質の介する代謝異常による網膜変性機構の解明
Author/Editor: 長田, 秀斗
Author Heading: 長田, 秀斗
Publication Date: 2020
Publication Date (W3CDTF): 2020
Alternative Title: シシツノカイスルタイシャイジョウニヨルモウマクヘンセイキコウノカイメイ
Shishitsu no kaisuru taisha ijō ni yoru mōmaku hensei kikō no kaimei
Elucidation of retinal degeneration mechanism due to lipid-mediated metabolic disorders
Periodical title: 科学研究費補助金研究成果報告書
Text Language Code: jpn
eng
Subject Heading: 網膜色素変性症
Target Audience: 一般
Note (General): type:text
代謝制御に寄与するアディポネクチン１型受容体(Adipor1)は機能阻害によって網膜色素変性症を呈することが知られているため、Adipor1ノックアウトマウスの網膜および血清を用いてリピドミクス解析を行った。網膜では視細胞外節の形成に重要なDHAを含む脂質の著しい低下を認めた。一方で血清中の脂肪酸の顕著な変化は認めなかった。視細胞内節において発現が認められる脂肪酸伸長酵素Elovl2の発現が低下していた。同時に、脂質合成に関与する多くの遺伝子群の発現が変化しており、Adipor1ノックアウトマウス網膜における局所的な脂質動態の変化が示唆された。 Lipid metabolism-related gene mutations can cause retinitis pigmentosa, a currently untreatable blinding disease resulting from progressive neurodegeneration of the retina. Here, we demonstrated the influence of adiponectin receptor 1 (ADIPOR1) deficiency in lipid metabolism and retinal neurodegeneration using Adipor1 knockout (KO) mice. Photoreceptors of KO mice were misaligned and their lipid composition, including DHA, which is critical in forming photoreceptor outer segments, was impaired in the retina. Importantly, the expression of Elovl2, an elongase of very long chain fatty acids, was significantly reduced, and lipogenic genes, which are induced under conditions of reduced endogenous DHA synthesis, were increased in KO mice. Therefore, ADIPOR1 in the retina appears to be indispensable for ELOVL2 induction, which is likely required in the retinal local lipid metabolism to supply sufficient DHA for appropriate photoreceptor function and survival.
研究種目 : 若手研究研究期間 : 2019～2020 課題番号 : 19K18854 研究分野 : 眼科学
Access Restrictions: 限定公開
Related Material: 科研費研究者番号 : 50748770
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 慶應義塾大学 : 慶應義塾大学学術情報リポジトリ