Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice 3

• 資料種別: 博士論文
• ISSN: 1932-6203
• タイトル: Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice
• 巻次・部編番号: 12 3
• 著者・編者: 髙原, 郁子
• 著者標目: 髙原, 郁子
• 出版事項: Public Library of Science
• 出版年月日等: 2020-09-02
• 出版年（W3CDTF）: 2020-09-02
• 並列タイトル等: トヨカマイシンは培養肝細胞における遊離脂肪酸が誘導する脂肪変性及びアポトーシスを抑制し、マウスにおける非アルコール性脂肪肝疾患を改善する
• タイトル（掲載誌）: PLOS ONE
• 授与機関名: Nagasaki University (長崎大学)
• 授与年月日: 2020-09-02
• 授与年月日（W3CDTF）: 2020-09-02
• 報告番号: 甲医歯薬第1273号
• 学位: 博士(医学)
• 博論授与番号: 甲医歯薬第1273号
• 本文の言語コード: eng
• 対象利用者: 一般
• 一般注記: Background and aims: A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD. Methods: Huh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed. Results: Toyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine-adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes. Conclusions: The data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans.; 長崎大学学位論文 学位記番号:博(医歯薬)甲第1273号 学位授与年月日:令和2年9月2日; Author: Ikuko Takahara, Yuko Akazawa, Maiko Tabuchi, Katsuya Matsuda, Hisamitsu Miyaaki, Youko Kido, Yasuko Kanda, Naota Taura, Ken Ohnita, Fuminao Takeshima, Yusuke Sakai, Susumu Eguchi, Masahiro Nakashima, Kazuhiko Nakao; Citation: PLOS ONE, 12(3), e0170591; 2017; identifier:Nagasaki University (長崎大学), 博士(医学) (2020-09-02); http://hdl.handle.net/10069/40344
• DOI: info:doi/10.1371/journal.pone.0170591; https://doi.org/info:doi/10.1371/journal.pone.0170591
• 国立国会図書館永続的識別子: info:ndljp/pid/11551966; https://dl.ndl.go.jp/pid/11551966
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2020-10-06T21:18:06+09:00
• 作成日（W3CDTF）: 2020-12-16
• 記録形式（IMT）: PDF
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 関連情報（URI）: http://hdl.handle.net/10069/40344
• 掲載誌（URI）: http://hdl.handle.net/10069/40279
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

目次

2021-03-07 再収集