Background and Aim: Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD) that characterised by the accumulation of lipids in the liver. Excessive intrahepatic lipid accumulation is associated with alteration of glucose, fatty acid metabolism and is known to drive inflammation and oxidative stress, ultimately leading to the development of hepatic and systemic insulin resistance. The aim of this study was to assess the effects of a nitroxide, Tempol, on the accumulation of lipid and inflammation induced by palmitic acid (PA) in human liver cells.
Methods and results: To assess the effects of Tempol, HepG2 cells were exposed to PA for 24 hours before exposure to Tempol (200µM, 500µM, 1mM, 2mM) for 5 hours. The effects of PA induced-cellular steatosis and inflammation were then assessed using an (i) oil red O staining and extraction method to assess lipid accumulation, (ii) RT-qPCR to assess the mRNA gene expression level of inflammatory markers, (iii) glycogen assay to assess glycogen levels (iv) dichlorofluorescein assay to assess reactive oxygen species (ROS) levels and (v) MTT assay to detect cell viability. The results show HepG2 exposed to TEMPOL reduced palmitic acid-induced- (i) lipid accumulation, (ii) inflammation, (iii) insulin-mediated glycogenesis and (iv) reactive oxygen species levels with (v) no effect on cell viability.
Conclusions: These findings suggest that Tempol plays a protective role in PA-induced hepatic steatosis that is associated with reduced hepatic inflammation, oxidative stress and insulin-mediated glycogenesis, thus indicating Tempol may be useful as a pharmaceutical therapy for improving hepatic steatosis and insulin sensitivity.