Bile Acid Sequestrant, Sevelamer Ameliorates Hepatic Fibrosis with Reduced Overload of Endogenous Lipopolysaccharide in Experimental Nonalcoholic Steatohepatitis. 6

• Material Type: 博士論文
• ISSN: 2076-2607
• Title: Bile Acid Sequestrant, Sevelamer Ameliorates Hepatic Fibrosis with Reduced Overload of Endogenous Lipopolysaccharide in Experimental Nonalcoholic Steatohepatitis.
• Volume: 8 6
• 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; 8 6
• 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
• Degree Grantor: 奈良県立医科大学
• Date Granted: 2021-03-15
• Date Granted (W3CDTF): 2021-03-15
• Dissertation Number: 甲第779号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第779号
• 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
• DOI: info:doi/10.3390/microorganisms8060925; https://doi.org/info:doi/10.3390/microorganisms8060925
• Persistent ID (NDL): info:ndljp/pid/12070982; https://dl.ndl.go.jp/pid/12070982
• 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): 2022-02-06T04:33:19+09:00
• Format (IMT): application/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
• Periodical Title (URI): http://hdl.handle.net/10564/3903
• 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

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