{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:23:17Z","timestamp":1791094997383,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T00:00:00Z","timestamp":1353888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>\n<jats:list>\n<jats:list-item><jats:p>Thiazolidinediones (<jats:styled-content style=\"fixed-case\">TZD<\/jats:styled-content>s) markedly reduce hepatic steatosis in both rodents and humans. However, the effects and mechanisms of action of <jats:styled-content style=\"fixed-case\">TZD<\/jats:styled-content>s on hepatic fibrosis remain unclear. The aim of the present study was to determine the effects of <jats:styled-content style=\"fixed-case\">TZD<\/jats:styled-content>s on histological changes in the liver and on the modulation by adiponectin via the <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\u2010activated protein kinase (<jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>) signalling pathway in rats with non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Forty rats were divided into normal control, high\u2010fat diet (<jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>), pioglitazone control and pioglitazone intervention groups. After 24\u00a0weeks treatment with pioglitazone (10\u00a0mg\/kg per day by gavage), changes in liver histology, serum aminotransaminase, triglyceride (<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>), free fatty acid (<jats:styled-content style=\"fixed-case\">FFA<\/jats:styled-content>), glucose, insulin, adiponectin and transforming growth factor (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>)\u2010\u03b21 concentrations and hepatic adiponectin, <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>, \u03b1\u2010smooth muscle actin (\u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) and collagen I expression were evaluated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The degree of hepatic steatosis and fibrosis was significantly higher in <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> rats compared with normal controls, as were serum concentrations of aminotransaminase, <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> FFA<\/jats:styled-content>, glucose, insulin and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21 and hepatic expression of \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> and collagen I protein. Serum adiponectin concentrations and hepatic expression of adiponectin <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> protein were significantly lower in the <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> rats compared with the normal control.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pioglitazone significantly reduced the degree of hepatic steatosis and fibrosis, as well as serum concentrations of aminotransaminase, <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> FFA<\/jats:styled-content>, glucose, insulin and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b21 and hepatic expression of \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> and collagen <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content> protein. In addition, pioglitazone significantly increased serum adiponectin concentrations and hepatic expression of adiponectin <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> protein.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, the <jats:styled-content style=\"fixed-case\">TZD<\/jats:styled-content> pioglitazone improved hepatic fibrosis in rats with <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> by upregulating adiponectin expression and activating <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>, thus subsequently inhibiting the activation of hepatic stellate cells and the overproduction of extracellular matrix.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/1440-1681.12020","type":"journal-article","created":{"date-parts":[[2012,11,6]],"date-time":"2012-11-06T10:32:52Z","timestamp":1352197972000},"page":"1026-1033","source":"Crossref","is-referenced-by-count":31,"title":["Thiazolidinediones improve hepatic fibrosis in rats with non\u2010alcoholic steatohepatitis by activating the adenosine monophosphate\u2010activated protein kinase signalling pathway"],"prefix":"10.1111","volume":"39","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Departments of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical University Chongqing 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