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

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 evalu...

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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
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Summary: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.
ISSN:1942-0900
1942-0994
DOI:10.1155/2018/5109503