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

• Material Type: 博士論文
• ISSN: 1932-6203
• Title: Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice
• Volume: 12 3
• Author/Editor: 髙原, 郁子
• Author Heading: 髙原, 郁子
• Publication, Distribution, etc.: Public Library of Science
• Publication Date: 2020-09-02
• Publication Date (W3CDTF): 2020-09-02
• Alternative Title: 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
• Periodical title: PLOS ONE
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2020-09-02
• Date Granted (W3CDTF): 2020-09-02
• Dissertation Number: 甲医歯薬第1273号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医歯薬第1273号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): 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
• Persistent ID (NDL): info:ndljp/pid/11551966; https://dl.ndl.go.jp/pid/11551966
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-10-06T21:18:06+09:00
• Date Created (W3CDTF): 2020-12-16
• Format (IMT): PDF
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Related Material (URI): http://hdl.handle.net/10069/40344
• Periodical Title (URI): http://hdl.handle.net/10069/40279
• Data Provider (Database): 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

Table of Contents

2021-03-07 再収集