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Antisteatotic effects of cerium oxide nanoparticles (CeO2NPs) have recently been shown in animal models of liver disease. However, it is unclear whether the activity of CeO2NPs is related solely to the decrease in oxidative stress or, in addition, they directly decrease liver fatty acid accumulation. To address this question, in this work, we used an in vitro model of hepatocellular steatosis, exposing HepG2 cells to oleic and palmitic acid. Cell uptake of CeO2NPs and their effect on oxidative stress and viability of hepatic cells cultured with H2O2 were also evaluated. Results show that CeO2NPs were uptaken by HepG2 cells and reduced oxidative stress and improved cell viability. Treatment with oleic and palmitic acid increased lipogenesis and the content of different fatty acids. CeO2NPs reduced palmitic and stearic acid and most fatty acids consisting of more than 18 carbon atoms. These effects were associated with significant changes in elongase and desaturase activity. In conclusion, CeO2NPs directly protected HepG2 cells from cell injury in oxidative stress conditions and reduced fatty acid content in steatotic conditions by inducing specific changes in fatty acid metabolism, thus showing potential in the treatment of NAFLD.<\/jats:p>","DOI":"10.3390\/biom9090425","type":"journal-article","created":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T11:26:22Z","timestamp":1567077982000},"page":"425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Beyond the Scavenging of Reactive Oxygen Species (ROS): Direct Effect of Cerium Oxide Nanoparticles in Reducing Fatty Acids Content in an In Vitro Model of Hepatocellular Steatosis"],"prefix":"10.3390","volume":"9","author":[{"given":"Marina","family":"Parra-Robert","sequence":"first","affiliation":[{"name":"Service of Biochemistry and Molecular Genetics, Hospital Clinic Universitari, Centro de Investigaci\u00f3n Biom\u00e9dica en 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Puntes","sequence":"additional","affiliation":[{"name":"Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"},{"name":"Institut Catal\u00e0 de Nanoci\u00e8ncia i Nanotecnologia (ICN2), CSIC, The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, 08193 Barcelona, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), 08010 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9376-0214","authenticated-orcid":false,"given":"Wladimiro","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Service of Biochemistry and Molecular Genetics, Hospital Clinic Universitari, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 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