Bile Acid Sequestrant, Sevelamer Ameliorates Hepatic Fibrosis with Reduced Overload of Endogenous Lipopolysaccharide in Experimental Nonalcoholic Steatohepatitis.

• Material Type: 博士論文
• Title: Bile Acid Sequestrant, Sevelamer Ameliorates Hepatic Fibrosis with Reduced Overload of Endogenous Lipopolysaccharide in Experimental Nonalcoholic Steatohepatitis.
• Author/Editor: Tsuji, Yuki; Kaji, Kosuke; Kitade, Mitsuteru; Kaya, Daisuke; Kitagawa, Koh; Ozutsumi, Takahiro; Fujinaga, Yukihisa; Takaya, Hiroaki; Kawaratani, Hideto; Namisaki, Tadashi; Moriya, Kei; Akahane, Takemi; Yoshiji, Hitoshi
• Author Heading: Tsuji, Yuki; Kaji, Kosuke; Kitade, Mitsuteru; Kaya, Daisuke; Kitagawa, Koh; Ozutsumi, Takahiro; Fujinaga, Yukihisa; Takaya, Hiroaki; Kawaratani, Hideto; Namisaki, Tadashi; Moriya, Kei; Akahane, Takemi; Yoshiji, Hitoshi
• Publication, Distribution, etc.: MDPI
• Publication Date: 2020-06-19
• Publication Date (W3CDTF): 2020-06-19
• Alternative Title: 胆汁酸吸着薬であるセベラマーは、内因性のリポポリサッカライドの過負荷を軽減して、非アルコール性脂肪性肝炎の肝線維化を改善する。
• Periodical title: Microorganisms
• No. or year of volume/issue: 8 6
• Volume: 8
• Issue: 6
• Pages: Article No.925-
• ISSN (Periodical Title): ISSN : 2076-2607
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2021-03-15
• Dissertation Number: 甲第779号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: nonalcoholic steatohepatitis; sevelamer; lipopolysaccharide; toll-like receptor 4
• Target Audience: 一般
• Note (General): type:Thesis; Despite the use of various pharmacotherapeutic strategies, fibrosis due to nonalcoholic steatohepatitis (NASH) remains an unsatisfied clinical issue. We investigated the effect of sevelamer, a hydrophilic bile acid sequestrant, on hepatic fibrosis in a murine NASH model. Male C57BL/6J mice were fed a choline-deficient, L-amino acid-defined, high-fat (CDHF) diet for 12 weeks with or without orally administered sevelamer hydrochloride (2% per diet weight). Histological and biochemical analyses revealed that sevelamer prevented hepatic steatosis, macrophage infiltration, and pericellular fibrosis in CDHF-fed mice. Sevelamer reduced the portal levels of total bile acid and inhibited both hepatic and intestinal farnesoid X receptor activation. Gut microbiome analysis demonstrated that sevelamer improved a lower α-diversity and prevented decreases in Lactobacillaceae and Clostridiaceae as well as increases in Desulfovibrionaceae and Enterobacteriaceae in the CDHF-fed mice. Additionally, sevelamer bound to lipopolysaccharide (LPS) in the intestinal lumen and promoted its fecal excretion. Consequently, the sevelamer treatment restored the tight intestinal junction proteins and reduced the portal LPS levels, leading to the suppression of hepatic toll-like receptor 4 signaling pathway. Furthermore, sevelamer inhibited the LPS-mediated induction of fibrogenic activity in human hepatic stellate cells in vitro. Collectively, sevelamer inhibited the development of murine steatohepatitis by reducing hepatic LPS overload.; 博士（医学）・甲第779号・令和3年3月15日; © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).; identifier:Microorganisms Vol.8 No.6 Article No.925 (2020 Jun); identifier:20762607; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3903; identifier:Microorganisms, 8(6): Article No.925
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3903/1/01%e7%94%b2779%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3903/2/02%e7%94%b2779%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3903/3/03%e7%94%b2779%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.3390/microorganisms8060925
• 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