Docosahexaenoic acid and hydroxytyrosol co‐administration fully prevents liver steatosis and related parameters in mice subjected to high‐fat diet: A molecular approach

• Published in: BioFactors (Oxford) 2019-11, Vol.45 (6), p.930-943
• Main Authors: Soto‐Alarcón, Sandra A., Ortiz, Macarena, Orellana, Paula, Echeverría, Francisca, Bustamante, Andrés, Espinosa, Alejandra, Illesca, Paola, Gonzalez‐Mañán, Daniel, Valenzuela, Rodrigo, Videla, Luis A.
• Format: Article
• Language: English
• Subjects: Animals; Diet, High-Fat - adverse effects; Dietary Supplements; Disease Models, Animal; docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; Drug Synergism; Fatty Liver - diet therapy; Fatty Liver - etiology; Fatty Liver - genetics; Fatty Liver - pathology; Humans; hydroxytyrosol; Inflammation - diet therapy; Inflammation - genetics; Inflammation - pathology; Lipid Metabolism - drug effects; Liver - drug effects; Liver - pathology; liver steatosis; Mice; oxidative stress; Oxidative Stress - drug effects; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; PPAR alpha - genetics; pro‐inflammatory status
• ISSN: 0951-6433; 1872-8081
• DOI: 10.1002/biof.1556

Attenuation of high‐fat diet (HFD)‐induced liver steatosis is accomplished by different nutritional interventions. Considering that the n‐3 PUFA docosahexaenoic acid (DHA) modulates lipid metabolism and the antioxidant hydroxytyrosol (HT) diminishes oxidative stress underlying fatty liver, it is hypothesized that HFD‐induced steatosis is suppressed by DHA and HT co‐administration. Male C57BL/6J mice were fed a control diet (CD; 10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks, without and with supplementation of DHA (50 mg/kg/day), HT (5 mg/kg/day) or both. The combined DHA + HT protocol fully prevented liver steatosis and the concomitant pro‐inflammatory state induced by HFD, with suppression of lipogenic and oxidative stress signaling, recovery of fatty acid oxidation capacity and enhancement in resolvin availability affording higher inflammation resolution capability. Abrogation of HFD‐induced hepatic steatosis by DHA and HT co‐administration represents a crucial therapeutic strategy eluding disease progression into stages lacking efficacious handling at present time.