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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3732

Title: Exogenous Administration of Low-Dose Lipopolysaccharide Potentiates Liver Fibrosis in a Choline-Deficient l-Amino-Acid-Defined Diet-Induced Murine Steatohepatitis Model.
Other Titles: リポポリサッカライドの外因性投与はコリン欠乏 L-アミノ酸置換食誘発脂肪性肝炎モデルマウスにおいて肝線維化を促進する
Authors: Nakanishi, Keisuke
Kaji, Kosuke
Kitade, Mitsuteru
Kubo, Takuya
Furukawa, Masanori
Saikawa, Soichiro
Shimozato, Naotaka
Sato, Shinya
Seki, Kenichiro
Kawaratani, Hideto
Moriya, Kei
Namisaki, Tadashi
Yoshiji, Hitoshi
Keywords: nonalcoholic steatohepatitis
lipopolysaccharide
choline-deficient l-amino-acid-defined diet
toll-like receptor
NF-κB
fibrosis
Issue Date: 3-Jun-2019
Publisher: MDPI
Citation: International journal of molecular sciences Vol.20 No.11 Article No.2724 (2019 Jun)
Abstract: Various rodent models have been proposed for basic research; however, the pathogenesis of human nonalcoholic steatohepatitis (NASH) is difficult to closely mimic. Lipopolysaccharide (LPS) has been reported to play a pivotal role in fibrosis development during NASH progression via activation of toll-like receptor 4 (TLR4) signaling. This study aimed to clarify the impact of low-dose LPS challenge on NASH pathological progression and to establish a novel murine NASH model. C57BL/6J mice were fed a choline-deficient l-amino-acid-defined (CDAA) diet to induce NASH, and low-dose LPS (0.5 mg/kg) was intraperitoneally injected thrice a week. CDAA-fed mice showed hepatic CD14 overexpression, and low-dose LPS challenge enhanced TLR4/NF-κB signaling activation in the liver of CDAA-fed mice. LPS challenge potentiated CDAA-diet-mediated insulin resistance, hepatic steatosis with upregulated lipogenic genes, and F4/80-positive macrophage infiltration with increased proinflammatory cytokines. It is noteworthy that LPS administration extensively boosted pericellular fibrosis with the activation of hepatic stellate cells in CDAA-fed mice. Exogenous LPS administration exacerbated pericellular fibrosis in CDAA-mediated steatohepatitis in mice. These findings suggest a key role for LPS/TLR4 signaling in NASH progression, and the authors therefore propose this as a suitable model to mimic human NASH.
Description: 博士(医学)・甲第738号・令和2年3月16日
© 2019 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/).
URI: http://hdl.handle.net/10564/3732
ISSN: 14220067
Academic Degrees and number: 24601A738
Degree-granting date: 2020-03-16
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2019年度

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