Olive Oil-derived Nitro-fatty Acids: Protection of Mitochondrial Function in Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive liver fat deposition in the absence of significant alcohol intake. Since extra virgin olive oil (EVOO) reduces fat accumulation, we analyzed the involvement of nitro-fatty acids (NO-FA) on the beneficial effects of EVOO consumption on NAFLD. Nitro-fatty acids formation was observed during digestion in mice supplemented with EVOO and nitrite. Mice fed with a high-fat diet (HF) presented lower plasma NO-FA levels than normal chow, and circulating concentrations recovered when the HF diet was supplemented with 10% EVOO plus nitrite. Under NO-FA formation conditions, liver hemoxygenase-1 expression significantly increased while decreased body weight and fat liver accumulation. Mitochondrial dysfunction plays a central role in the pathogenesis of NAFLD while NO-FA has been shown to protect from mitochondrial oxidative damage. Accordingly, an improvement of respiratory indexes was observed when mice were supplemented with both EVOO plus nitrite. Liver mitochondrial complexes II and V activities were greater in mice with EVOO supplementation and further improved in the presence of nitrite. Overall, our results strongly suggest a positive correlation between NO-OA formation from EVOO and the observed improvement of mitochondrial function in NAFLD. The formation of NO-FA can account for the health benefits associated with EVOO consumption.