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腸-肝連関を介したセロトニンの非アルコール性脂肪肝の病態への関与
http://hdl.handle.net/10191/0002000461
http://hdl.handle.net/10191/00020004610b0ae01f-0d65-4c2c-b663-2b87513a4c37
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本文 (17.47MB)
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要旨 (437KB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2022-05-10 | |||||||||
| タイトル | ||||||||||
| タイトル | Modulation of serotonin in the gut–liver neural axis ameliorates the fatty and fibrotic changes in nonalcoholic fatty liver | |||||||||
| 言語 | en | |||||||||
| タイトル | ||||||||||
| タイトル | 腸-肝連関を介したセロトニンの非アルコール性脂肪肝の病態への関与 | |||||||||
| 言語 | ja | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Fatty liver | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Autonomic neuron | |||||||||
| 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 | Diet | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | Hormone | |||||||||
| 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 |
髙, 昌良
× 髙, 昌良
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| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect ofmodulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD. | |||||||||
| 言語 | en | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | Disease models & mechanisms. 2021, 14(3), dmm048922 | |||||||||
| 言語 | en | |||||||||
| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | https://doi.org/10.1242/dmm.048922 | |||||||||
| 権利 | ||||||||||
| 言語 | en | |||||||||
| 権利情報 | 【○!C】 2021. Published by The Company of Biologists Ltd | |||||||||
| 権利 | ||||||||||
| 言語 | en | |||||||||
| 権利情報Resource | https://creativecommons.org/licenses/by/4.0/ | |||||||||
| 権利情報 | Creative Commons Attribution 4.0 International | |||||||||
| 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 | 13101 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 新潟大学 | |||||||||
| 言語 | en | |||||||||
| 学位授与機関名 | Niigata University | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2021-09-21 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第4929号 | |||||||||
| 学位記番号 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | 新大院博(医)第1019号 | |||||||||
| 言語 | ja | |||||||||
