Beyond the scavenging of reactive oxygen species (ROS): direct efect of cerium oxide nanoparticles in reducing fatty acids content in an in vitro model of hepatocellular steatosis

Abstract

Cerium oxide nanoparticles; Oxidative stress; Nonalcoholic fatty liver disease

Nanopartículas de óxido de cerio; Estrés oxidativo; Enfermedad del hígado graso no alcohólico

Nanopartícules d’òxid de ceri; Estrès oxidatiu; Malalties hepàtiques no alcohòliques

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipids. 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.

This research was funded by Ministerio de Economía y Competitividad, grant number PI15-00077 to G.C. and SAF2016-75358-R to M.M-R., co-financed by FEDER, European Union, “A way of making Europe”.; “Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya, convocatòria d’Indústria del Coneixement modalitat B”, grant number 2018_PROD_00187 toW.J, cofinanced by the European Union through the European Regional Development Fund (ERDF), “A way of making Europe”.; CIBERehd is financed by the Instituto de Salud Carlos III.;Wuyi University Funding for Hight Talents Introduction, grant number 2018TP010 to E.C. and 2018TP011 to M.Z.; Foundation from Department of Education of Guangdong Province, grant number 2016KCXTD005 and 2017KSYS010, to E.C. and M.Z. The APC was funded by Wuyi University Funding for Hight Talents Introduction, grant number 2018TP010 to E.C.