{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:15:54Z","timestamp":1791908154785,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T00:00:00Z","timestamp":1513209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Non\u2010alcoholic fatty liver disease (<jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>) and non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>) are common clinico\u2010pathological conditions that affect millions of patients worldwide. In this study, the efficacy of saroglitazar, a novel <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1\/\u03b3 agonist, was assessed in models of <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods &amp; Results<\/jats:title><jats:p>HepG2 cells treated with palmitic acid (<jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>;0.75 <jats:styled-content style=\"fixed-case\">mM<\/jats:styled-content>) showed decreased expression of various antioxidant biomarkers (<jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content>2, glutathione peroxidase and catalase) and increased expression of inflammatory markers (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>1\u03b2 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>6). These effects were blocked by saroglitazar, pioglitazone and fenofibrate (all tested at 10\u03bcM concentration). Furthermore, these agents reversed <jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>\u2010mediated changes in mitochondrial dysfunction, <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> production, <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>kB phosphorylation and stellate cell activation in HepG2 and HepG2\u2010<jats:styled-content style=\"fixed-case\">LX<\/jats:styled-content>2 Coculture studies. In mice with choline\u2010deficient high\u2010fat diet\u2010induced <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>, saroglitazar reduced hepatic steatosis, inflammation, ballooning and prevented development of fibrosis. It also reduced serum alanine aminotransferase, aspartate aminotransferase and expression of inflammatory and fibrosis biomarkers. In this model, the reduction in the overall <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> activity score by saroglitazar (3\u00a0mg\/kg) was significantly more prominent than pioglitazone (25\u00a0mg\/kg) and fenofibrate (100\u00a0mg\/kg). Pioglitazone and fenofibrate did not show any improvement in steatosis, but partially improved inflammation and liver function. Antifibrotic effect of saroglitazar (4\u00a0mg\/kg) was also observed in carbon tetrachloride\u2010induced fibrosis model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Saroglitazar, a dual <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1\/\u03b3 agonist with predominant <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 activity, shows an overall improvement in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>. The effects of saroglitazar appear better than pure <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 agonist, fenofibrate and <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b3 agonist pioglitazone.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13634","type":"journal-article","created":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T02:12:50Z","timestamp":1511316770000},"page":"1084-1094","source":"Crossref","is-referenced-by-count":202,"title":["Dual <scp>PPAR<\/scp>\u03b1\/\u03b3 agonist saroglitazar improves liver histopathology and biochemistry in experimental <scp>NASH<\/scp> models"],"prefix":"10.1111","volume":"38","author":[{"given":"Mukul R.","family":"Jain","sequence":"first","affiliation":[{"name":"Zydus Research Centre Cadila Healthcare Limited  Ahmedabad Gujarat India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh R.","family":"Giri","sequence":"additional","affiliation":[{"name":"Zydus Research 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Sankar","family":"Roy","sequence":"additional","affiliation":[{"name":"Cell Biology and Physiology Division Indian Institute of Chemical Biology  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabanita","family":"Das","sequence":"additional","affiliation":[{"name":"Cell Biology and Physiology Division Indian Institute of Chemical Biology  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eshani","family":"Karmakar","sequence":"additional","affiliation":[{"name":"Cell Biology and Physiology Division Indian Institute of Chemical Biology  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Wahli","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Zydus Research 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