Abstract

Non-alcoholic fatty liver disease (NAFLD) is directly associated with insulin resistance and oxidative stress. In NAFLD is established a reduction in n-3 LCPUFA (EPA + DHA) levels and hepatic activity of transcription factor PPAR-α. EPA and DHA inhibit lipogenesis and stimulate fatty acid oxidation in the liver. Extra virgin olive oil (EVOO) has important antioxidant properties. This study evaluated the prevention of insulin resistance and prevention of depletion of hepatic antioxidant defense in C57BL/6J mice fed high-fat diet (HFD), supplemented with n-3 LCPUFA plus EVOO. HFD generated insulin resistance and hepatic steatosis, together with significant reduction in i) n-3 LCPUFA hepatic levels, ii) DNA binding activity of PPAR-α, iii) activity of antioxidant enzymes (catalase and supero- xide dismutase), respect to control group (fed with control diet). Supplementation with n-3 LCPUFA plus EVOO prevent development insulin resistance and attenuate increased of fat in liver (p < 0.05), together with a normalization of i) DNA binding activity of PPAR-α, ii) activity of antioxidant enzymes (catalase and superoxide dismutase) and iii) reducing depletion of n-3 LCPUFA levels in liver tissue, compared to the control group (p < 0.05). Supplementation with n-3 LCPUFA plus EVOO reduced hepatic steatosis and prevent development of insulin resistance, along with preserving the antioxidant defense in liver. Projecting the use of this mixture of AGPICL n-3 plus EVOO as a potential treatment of NAFLD.