Abstract
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.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation, mainly in the form of triglycerides, and covers a wide spectrum of liver disease that ranges from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), the last being
The current study shows that CeO2 NPs present protective cellular effects and reduce fatty acids (FAs) content in cultured human hepatic cells (HepG2 cells) cultivated under characteristic conditions of NAFLD
Cells were cultured under oxidative stress (H2 O2 induced) or steatosis (OA:palmitic acid (PA) induced) in order to evaluate if CeO2 NPs presented a direct effect in these specific conditions
Summary
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation (steatosis), mainly in the form of triglycerides, and covers a wide spectrum of liver disease that ranges from simple hepatic steatosis (nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), the last beingBiomolecules 2019, 9, 425; doi:10.3390/biom9090425 www.mdpi.com/journal/biomoleculesBiomolecules 2019, 9, 425 characterized by the appearance of inflammation and a higher risk of progression to more advanced forms including fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [1].Oxidative stress plays a role in the molecular mechanisms behind the progression of NAFLD. The multiple-hit hypothesis considers multiple insults, including insulin resistance, adipokines, nutritional factors or gut microbiota that act together on genetically predisposed subjects in the development and progression of the disease [2,3]. These insults are associated with increased oxidative stress, proinflammatory cytokines and adipocytokines, leading to hepatocyte injury, inflammation and fibrosis [4,5]. The hepatic accumulation of free FA, lipid peroxidation products (reactive aldehydes and oxysterols) and reactive oxygen species (ROS) contribute to the development and progression of NAFLD from simple steatosis to NASH by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury [6,7]
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