Oral administration of fructose exacerbates liver fibrosis and hepatocarcinogenesis via increased intestinal permeability in a rat steatohepatitis model.

• Material Type: 博士論文
• Title: Oral administration of fructose exacerbates liver fibrosis and hepatocarcinogenesis via increased intestinal permeability in a rat steatohepatitis model.
• Author/Editor: Seki, Kenichiro; Kitade, Mitsuteru; Nishimura, Norihisa; Kaji, Kosuke; Asada, Kiyoshi; Namisaki, Tadashi; Moriya, Kei; Kawaratani, Hideto; Okura, Yasushi; Takaya, Hiroaki; Sawada, Yasuhiko; Sato, Shinya; Nakanishi, Keisuke; Yoshiji, Hitoshi
• Author Heading: Seki, Kenichiro; Kitade, Mitsuteru; Nishimura, Norihisa; Kaji, Kosuke; Asada, Kiyoshi; Namisaki, Tadashi; Moriya, Kei; Kawaratani, Hideto; Okura, Yasushi; Takaya, Hiroaki; Sawada, Yasuhiko; Sato, Shinya; Nakanishi, Keisuke; Yoshiji, Hitoshi
• Publication, Distribution, etc.: Impact Journals
• Publication Date: 2018-06-19
• Publication Date (W3CDTF): 2018-06-19
• Alternative Title: フルクトースの経口投与はラット脂肪性肝炎モデルにおいて腸管透過性亢進作用を介して肝線維化および肝発癌を悪化させる
• Periodical title: Oncotarget
• No. or year of volume/issue: 9 47
• Volume: 9
• Issue: 47
• Pages: 28638-28651
• ISSN (Periodical Title): ISSN : 1949-2553
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2019-09-27
• Dissertation Number: 乙第1432号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: non-alcoholic steatohepatitis (NASH); fructose; hepatocarcinogenesis; intestinal permeability; endotoxin
• Target Audience: 一般
• Note (General): type:Thesis; Recent reports have revealed the impact of a western diet containing large amounts of fructose on the pathogenesis of non-alcoholic steatohepatitis (NASH). Fructose exacerbates hepatic inflammation in NASH by inducing increasing intestinal permeability. However, it is not clear whether fructose contributes to the progression of liver fibrosis and hepatocarcinogenesis in NASH. The aim of this study was to investigate the effect of fructose intake on NASH in a rat model. A choline-deficient/L-amino acid diet was fed to F344 rats to induce NASH. Fructose was administrated to one group in the drinking water. The development of liver fibrosis and hepatocarcinogenesis were evaluated histologically. Oral fructose administration exacerbated liver fibrosis and increased the number of preneoplastic lesions positive for glutathione S-transferase placental form. Fructose-treated rats had significantly higher expression of hepatic genes related to toll-like receptor-signaling, suggesting that fructose consumption increased signaling in this pathway, leading to the progression of NASH. We confirmed that intestinal permeability was significantly higher in fructose-treated rats, as evidenced by a loss of intestinal tight junction proteins. Fructose exacerbated both liver fibrosis and hepatocarcinogenesis by increasing intestinal permeability. This observation strongly supports the role of endotoxin in the progression of NASH.; 博士（医学）・乙第1432号・令和元年9月27日; Copyright © 2018 Impact Journals, LLC; Copyright © Seki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0 https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.; identifier:Oncotarget Vol.9 No.47 p.28638-28651 (2018 Jun); identifier:19492553; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3668; identifier:Oncotarget, 9(47): 28638-28651
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3668/1/011432.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3668/2/021432.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3668/3/031432.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.18632/oncotarget.25587
• 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): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU