{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T12:11:29Z","timestamp":1781093489862,"version":"3.54.1"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T00:00:00Z","timestamp":1559520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-\u03baB 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.<\/jats:p>","DOI":"10.3390\/ijms20112724","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T11:31:01Z","timestamp":1559561461000},"page":"2724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Exogenous Administration of Low-Dose Lipopolysaccharide Potentiates Liver Fibrosis in a Choline-Deficient l-Amino-Acid-Defined Diet-Induced Murine Steatohepatitis Model"],"prefix":"10.3390","volume":"20","author":[{"given":"Keisuke","family":"Nakanishi","sequence":"first","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Kaji","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuteru","family":"Kitade","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Kubo","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Saikawa","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotaka","family":"Shimozato","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Sato","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Seki","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-0592","authenticated-orcid":false,"given":"Hideto","family":"Kawaratani","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Moriya","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Namisaki","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Yoshiji","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1002\/hep.20973","article-title":"Nonalcoholic fatty liver disease: From steatosis to cirrhosis","volume":"43","author":"Farrell","year":"2006","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1056\/NEJMra011775","article-title":"Nonalcoholic Fatty Liver Disease","volume":"346","author":"Angulo","year":"2002","journal-title":"N. 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