Attenuation of High-Fat Diet-Induced Rat Liver Oxidative Stress and Steatosis by Combined Hydroxytyrosol- (HT-) Eicosapentaenoic Acid Supplementation Mainly Relies on HT

• Published in: Oxidative medicine and cellular longevity 2018-01, Vol.2018 (2018), p.1-13
• Main Authors: Videla, Luis A., Corbari, Alicia, Soto-Alarcon, Sandra A., Ortiz, Macarena, Álvarez, Daniela, Bustamante, Andrés, Valenzuela, R., Echeverría, Francisca, Muñoz, Patricio
• Format: Article
• Language: English
• Subjects: Antioxidants; Cardiovascular disease; Chemistry; Diet; Drug dosages; Endoplasmic reticulum; Fatty acids; Hepatology; Inflammation; Insulin resistance; Laboratory animals; Liver diseases; Nutrition research; Omega-3 fatty acids; Oxidative stress; Pharmaceutical industry; Physiological aspects; Proteins; Rodents; Unsaturated fatty acids
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2018/5109503

Pharmacological therapy for nonalcoholic fatty liver disease (NAFLD) is not approved at the present time. For this purpose, the effect of combined eicosapentaenoic acid (EPA; 50 mg/kg/day) modulating hepatic lipid metabolism and hydroxytyrosol (HT; 5 mg/kg/day) exerting antioxidant actions was evaluated on hepatic steatosis and oxidative stress induced by a high-fat diet (HFD; 60% fat, 20% protein, and 20% carbohydrates) compared to a control diet (CD; 10% fat, 20% protein, and 70% carbohydrates) in mice fed for 12 weeks. HFD-induced liver steatosis (i) was reduced by 32% by EPA, without changes in oxidative stress-related parameters and mild recovery of Nrf2 functioning affording antioxidation and (ii) was decreased by 42% by HT, concomitantly with total regain of the glutathione status diminished by HFD, 42% to 59% recovery of lipid peroxidation and protein oxidation enhanced by HFD, and regain of Nrf2 functioning, whereas (iii) combined EPA + HT supplementation elicited 74% reduction in liver steatosis, with total recovery of the antioxidant potential in a similar manner than HT. It is concluded that combined HT + EPA drastically decreases NAFLD development, an effect that shows additivity in HT and EPA effects that mainly relies on HT, strengthening the impact of oxidative stress as a central mechanism underlying liver steatosis in obesity.