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Since human steatohepatitis (both the alcoholic\u00a0and non-alcoholic type) is characterized by reduced expression of PPAR\u03b1 and disturbed lipid metabolism we investigated the role of this ligand-activated receptor in the development of DDC-induced liver injury. Acute DDC-intoxication was accompanied by early significant downregulation of<jats:italic>Ppar\u03b1<\/jats:italic>mRNA expression along with PPAR\u03b1-controlled stress-response and lipid metabolism genes that persisted in the chronic stage. Administration of the specific PPAR\u03b1 agonist fenofibrate together with DDC prevented the downregulation of PPAR\u03b1-associated genes and also improved the stress response of Nrf2-dependent redox-regulating genes. Moreover, oxidative stress and inflammation were strongly reduced by DDC\/fenofibrate co-treatment. In addition, fenofibrate prevented the disruption of hepatocyte intermediate filament cytoskeleton and the formation of Mallory-Denk bodies at late stages of DDC intoxication. Our findings show that, like in human steatohepatitis, PPAR\u03b1 is downregulated in the DDC model of steatohepatitis-like hepatocellular damage. Its downregulation and the pathomorphologic features of steatohepatitis are prevented by co-administration of fenofibrate.<\/jats:p>","DOI":"10.1038\/s41598-018-31389-3","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T10:24:58Z","timestamp":1534933498000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The PPAR\u03b1 Agonist Fenofibrate Prevents Formation of Protein Aggregates (Mallory-Denk bodies) in a Murine Model of Steatohepatitis-like Hepatotoxicity"],"prefix":"10.1038","volume":"8","author":[{"given":"Aniket","family":"Nikam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay V.","family":"Patankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghana","family":"Somlapura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Lahiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay","family":"Sachdev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1357-7573","authenticated-orcid":false,"given":"Dagmar","family":"Kratky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Denk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5299-7218","authenticated-orcid":false,"given":"Kurt","family":"Zatloukal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Abuja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,8,28]]},"reference":[{"key":"31389_CR1","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1056\/NEJMra011775","volume":"346","author":"P Angulo","year":"2002","unstructured":"Angulo, P. 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