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O-GlcNAc modification in endothelial cells modulates adiposity via fat absorption from the intestine in mice
http://hdl.handle.net/10422/0002000473
http://hdl.handle.net/10422/00020004735756034b-2319-407e-b5ca-70f8cebeacee
Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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公開日 | 2025-06-17 | |||||||||
タイトル | ||||||||||
タイトル | O-GlcNAc modification in endothelial cells modulates adiposity via fat absorption from the intestine in mice | |||||||||
言語 | en | |||||||||
言語 | ||||||||||
言語 | eng | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Obesity | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Endothelial cell | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | O-GlcNAcylation | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Lipid absorption | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Vascular endothelial growth factor receptor 3 | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Nitric oxide | |||||||||
資源タイプ | ||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
資源タイプ | doctoral thesis | |||||||||
アクセス権 | ||||||||||
アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
著者 |
Ohgaku, Seiichiro
× Ohgaku, Seiichiro |
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著者別名 |
大⻆, 誠一郎
× 大⻆, 誠一郎
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抄録 | ||||||||||
内容記述タイプ | Abstract | |||||||||
内容記述 | Introduction Endothelial cells have a crucial function in transporting and exchanging various nutrients. O-GlcNAcylation, mediated by O-GlcNAc transferase (OGT), involves the addition of N-acetylglucosamine to proteins and serves as an intracellular nutrient sensing mechanism. However, the role of O-GlcNAcylation in endothelial cells remains poorly understood. Objective This study investigated the role of O-GlcNAcylation in endothelial cells. Methods Endothelial-cell-specific Ogt -knockout mice (Ogt-ECKO) were generated by crossing Ogt-floxed mice (Ogt-flox) with VE-Cadherin Cre ERT2 mice. Ogt-ECKO mice and Ogt-flox control mice were subjected to a normal or high-fat diet, and their body weight, glucose metabolism, and lipid metabolism were examined. Results Ogt-ECKO mice exhibited reduced body weight compared with Ogt-flox control mice under a high-fat diet. Lipid absorption was significantly impaired in Ogt-ECKO mice. Changes in the intercellular junctions of small intestinal lacteal endothelial cells from a button-like to a zipper-like configuration were observed. Furthermore, Ogt-ECKO mice showed decreased expression of VEGFR3. The administration of a nitric oxide donor restored lipid absorption and reversed the morphological alterations in Ogt-ECKO mice. Conclusions These findings demonstrate the critical role of O-GlcNAcylation in endothelial cells in lipid absorption in the intestine through the modulation of lacteal junction morphology. These results provide novel insight into the metabolic regulatory mechanisms under physiological conditions and have implications for the development of new therapeutic strategies for obesity. |
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言語 | en | |||||||||
学位名 | ||||||||||
言語 | ja | |||||||||
学位名 | 博士(医学) | |||||||||
学位授与機関 | ||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||
学位授与機関識別子 | 14202 | |||||||||
言語 | ja | |||||||||
学位授与機関名 | 滋賀医科大学 | |||||||||
学位授与年度 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | 令和6年度 | |||||||||
言語 | ja | |||||||||
学位授与年月日 | ||||||||||
学位授与年月日 | 2025-03-21 | |||||||||
学位授与番号 | ||||||||||
学位授与番号 | 甲第1020号 | |||||||||
書誌情報 |
en : Heliyon 巻 10, 号 14, p. e34490, 発行日 2024-07-14 |
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出版者 | ||||||||||
出版者 | Elsevier | |||||||||
言語 | en | |||||||||
著者版フラグ | ||||||||||
出版タイプ | VoR | |||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
ISSN | ||||||||||
収録物識別子タイプ | ISSN | |||||||||
収録物識別子 | 2405-8440 | |||||||||
PMID | ||||||||||
識別子タイプ | PMID | |||||||||
関連識別子 | 39130439 | |||||||||
DOI | ||||||||||
関連タイプ | isIdenticalTo | |||||||||
識別子タイプ | DOI | |||||||||
関連識別子 | https://doi.org/10.1016/j.heliyon.2024.e34490 |