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Mol Nutr Food Res. 2017 Dec;61(12). doi: 10.1002/mnfr.201700479. Epub 2017 Nov 13.

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.

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Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile.
Lipid Center, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile.
Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago, Chile.
Department of Biochemistry, School of Biochemistry, University of Litoral, Santa Fe, Argentina.
Faculty of Chemical Sciences and Pharmacy, Department of Food Science and Chemical Technology, University of Chile, Santiago, Chile.
Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, University of Chile, Santiago, Chile.



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.


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.


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.


docosahexaenoic acid; extra virgin olive oil; nuclear factor E2-related factor 2; nuclear factor-κB; peroxisome proliferator-activated receptor-α; sterol regulatory element-binding protein 1c

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