{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T01:17:49Z","timestamp":1782177469022,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["26861059"],"award-info":[{"award-number":["26861059"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["16K10489"],"award-info":[{"award-number":["16K10489"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>Although several non\u2010alcoholic steatohepatitis (NASH) models have been reported to date, few of these models fully reflect the histopathology and pathophysiology of human NASH. The aim of this study was to establish a novel NASH model by feeding a high\u2010fat (HF) diet and administering both carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) and the Liver X receptor agonist T0901317. Male C57BL\/6J mice were divided into four groups (each n\u2009=\u20095): HF, HF\u2009+\u2009CCl<jats:sub>4<\/jats:sub>, HF\u2009+\u2009T0901317, and the novel NASH model (HF\u2009+\u2009CCl<jats:sub>4<\/jats:sub>\u2009+\u2009T0901317). CCl<jats:sub>4<\/jats:sub> (0.1\u2009mL\/kg) and T0901317 (2.5\u2009mg\/kg) were intraperitoneally administered four times and five times, respectively. The livers of the novel NASH model group presented a whitish colour. The serum levels of TNF\u2010\u03b1 and IL\u20106 were significantly increased in the novel NASH model group, and mice in this group exhibited histopathological features and insulin resistance reflective of NASH, i.e., macrovesicular hepatic steatosis, ballooning hepatocytes, Mallory\u2010Denk bodies, lobular inflammation and fibrosis. The novel NASH model group presented significantly upregulated expression levels of mRNAs related to lipogenesis, oxidative stress, fibrosis and steatosis and significantly downregulated expression levels of mRNAs related to triglyceride export. We successfully established a novel experimental NASH model that exhibits similar histopathology and pathophysiology to human NASH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pin.12612","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T10:42:51Z","timestamp":1511174571000},"page":"12-22","source":"Crossref","is-referenced-by-count":24,"title":["Novel non\u2010alcoholic steatohepatitis model with histopathological and insulin\u2010resistant features"],"prefix":"10.1111","volume":"68","author":[{"given":"Yohei","family":"Owada","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohito","family":"Tanoi","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuji","family":"Hisakura","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsuzaka","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Shimano","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"},{"name":"International Institute for Integrative Sleep Medicine (WPI\u2010IIIS) University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"},{"name":"AMED\u2010CREST Japan Agency for Medical Research and Development (AMED) 1\u20107\u20101, Ohte\u2010machi Chiyoda\u2010ku Tokyo, 100\u20100004 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1133-3313","authenticated-orcid":false,"given":"Shingo","family":"Sakashita","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Matsukawa","sequence":"additional","affiliation":[{"name":"Graduate School of Environmental Sciences University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108572 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Isoda","sequence":"additional","affiliation":[{"name":"Graduate School of Environmental Sciences University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108572 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Ohkohchi","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Faculty of Medicine University of Tsukuba 1\u20101\u20101 Tennodai Tsukuba 305\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50161"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v7.i17.2110"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20466"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2003.03252.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04724.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-012-0533-z"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20877"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.56.263"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2008.05543.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hepres.2005.09.022"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81294-5"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2007.05004.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20170"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8814"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i19.2300"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2007.00008.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01357-3"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-012-9429-3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12607"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70599-2"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i48.18070"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2005.01191.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.071118"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v7.i6.846"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30692"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-14-0182"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270515"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.12.3391"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301977200"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210689200"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.11.2784"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.06.011"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24001"},{"key":"e_1_2_7_36_1","first-page":"5196","article-title":"Identification of Nrf2\u2010regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray","volume":"62","author":"Thimmulappa RK","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3797"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.2007.S143"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2010.95"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.90339.2008"}],"container-title":["Pathology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpin.12612","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/chorus\/v1\/articles\/10.1111%2Fpin.12612","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.12612","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T14:48:24Z","timestamp":1695998904000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.12612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,20]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1111\/pin.12612"],"URL":"https:\/\/doi.org\/10.1111\/pin.12612","archive":["Portico"],"relation":{},"ISSN":["1320-5463","1440-1827"],"issn-type":[{"value":"1320-5463","type":"print"},{"value":"1440-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,20]]}}}