Supplementation with Docosahexaenoic Acid and Extra Virgin Olive Oil Prevents Liver Steatosis Induced by a High‐Fat Diet in Mice through PPAR‐α and Nrf2 Upregulation with Concomitant SREBP‐1c and NF‐kB Downregulation

Scope Nonalcoholic fatty liver disease is the most common cause of liver disease, for which there is no validated drug therapy at present time. In this respect, the PUFA docosahexaenoic acid (DHA; C22:6 n‐3) modulate lipid metabolism in the liver, and extra virgin olive oil (EVOO) has hepatoprotective effects. Methods and results The effect of combined DHA (C22:6 n‐3) and EVOO administration to mice on oxidative stress and metabolic disturbances induced by high‐fat diet (HFD) is evaluated. Male C57BL/6J mice are fed with a control diet (10% fat, 20% protein, and 70% carbohydrates) or an HFD (60% fat, 20% protein, and 20% carbohydrates) for 12 weeks. Animals are supplemented with DHA (50 mg/kg/day), EVOO (50 mg/kg/day), or DHA + EVOO through oral route. DHA + EVOO cosupplementation results in greater protection ( p < 0.05) over that elicited by DHA or EVOO supply alone, when compared to the damage induced by HFD. DHA + EVOO significantly reduces hepatic steatosis, oxidative stress, systemic inflammation, and insulin resistance. Conclusion Synergistic beneficial effects of DHA + EVOO supplementation are associated with the activation/inactivation of key transcription factors involved in the above‐mentioned processes. Data presented indicate that dietary supplementation with DHA + EVOO drastically reduces the development of nonalcoholic fatty liver disease.