{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:30:00Z","timestamp":1771655400328,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T00:00:00Z","timestamp":1471392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Low\u2010density lipoprotein receptor knockout (LDLR\u2010KO) mice fed a modified choline\u2010deficient and amino acid\u2010defined (mCDAA) diet show non\u2010alcoholic steatohepatitis (NASH)\u2010like pathophysiology. In order to pharmacologically benchmark this model, effects of pioglitazone (a thiazolidinedione) and candesartan cilexetil (an angiotensin II type 1 receptor blocker) on steatosis and liver fibrosis were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pioglitazone (10\u00a0mg\/kg) and candesartan cilexetil (3\u00a0mg\/kg) were given orally once daily to LDLR\u2010KO mice under mCDAA diet for 7\u00a0weeks. Blood biochemistry and hepatic histology were assessed, and hepatic gene expression levels and triglyceride content were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pioglitazone suppressed hepatic <jats:italic>COL1A1<\/jats:italic> gene expression by 43% and attenuated hepatic fibrosis areas by 49%. Pioglitazone also decreased plasma alanine aminotransferase levels, liver weight, hepatic triglyceride content, and hepatic expression of other fibrosis\u2010related genes such as <jats:italic>TGFB1<\/jats:italic>, <jats:italic>SPP1<\/jats:italic>, <jats:italic>TIMP1<\/jats:italic>, and <jats:italic>IL6<\/jats:italic>. Candesartan cilexetil suppressed hepatic <jats:italic>COL1A1<\/jats:italic> gene expression by 33%, whereas the other end\u2010points including hepatic fibrosis areas were not affected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pioglitazone showed anti\u2010fibrotic effects accompanied by improving hepatic transaminase activity and hepatic lipid accumulation, but the effect of candesartan cilexetil was only limited, unlike previous reports for angiotensin II type 1 receptor blockers. As the pharmacological effects of pioglitazone in the current animal model are similar to those reported in patients with NASH, this model may represent some aspects of the pathophysiology of NASH. Further profiling using other agents or mechanisms that have been tested in the clinic will better clarify the utility of the animal model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12773","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T15:24:13Z","timestamp":1468596253000},"page":"584-592","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological evaluation of pioglitazone and candesartan cilexetil in a novel mouse model of non\u2010alcoholic steatohepatitis, modified choline\u2010deficient, amino acid\u2010defined diet fed low\u2010density lipoprotein receptor knockout mice"],"prefix":"10.1111","volume":"47","author":[{"given":"Shuntarou","family":"Tsuchiya","sequence":"first","affiliation":[{"name":"Pharmaceutical Research Division Takeda Pharmaceutical Company Limited  Fujisawa 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