title: Anti-steatotic effects of an n-3 LCPUFA and extra virgin olive oil mixture in the liver of mice subjected to high-fat diet.
abstract: Non-alcoholic fatty liver disease (NAFLD) is characterized by liver steatosis, oxidative stress, and drastic depletion of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), namely, eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA), which trigger lipolysis stimulation and lipogenesis inhibition. Extra virgin olive oil (EVOO) has important antioxidant effects. This study evaluated the anti-steatotic effects of n-3 LCPUFA plus EVOO in the liver of male C57BL/6J mice subjected to a control diet (CD) (10% fat, 20% protein, 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, 20% carbohydrate), without and with supplementation with n-3 LCPUFA (100 mg per kg per day) plus EVOO (100 mg per kg per day) for 12 weeks. HFD induced (i) liver steatosis (increased total fat, triacylglycerols, and free fatty acid total contents), (ii) higher fasting serum glucose and insulin levels and HOMA index, total cholesterol, triacylglycerols and TNF-α and IL-6, (iii) liver and plasma oxidative stress enhancement, (iv) depletion of the n-3 LCPUFA hepatic content, and (v) increment in lipogenic enzyme activity and reduction in lipolytic enzyme activity. These changes were either reduced (p < 0.05) or normalized to control the values in animals subjected to HFD supplemented with n-3 LCPUFA plus EVOO. In conclusion, n-3 LCPUFA plus EVOO intervention exerts anti-steatotic effects underlying antioxidant and anti-inflammatory responses, improved insulin sensitivity, and recovery of the lipolytic/lipogenic status of the liver altered by HFD, and supports the potential therapeutic use of n-3 LCPUFA plus EVOO supplementation in the treatment of human liver steatosis induced by nutritional factors or other etiologies.
authors.affiliation: Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Valenzuela
authors.affiliation: Medical Technology Department, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Espinosa
authors.affiliation: Institute for Research in Dental Sciences, Faculty of Dentistry, University of Chile, Santiago, Chile.
authors.forename: Paola
authors.initials: P
authors.lastname: Llanos
authors.affiliation: Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.
authors.forename: Maria Catalina
authors.initials: MC
authors.lastname: Hernandez-Rodas
authors.affiliation: Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Barrera
authors.affiliation: Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vergara
authors.affiliation: Faculty of Chemical Sciences and Pharmacy, Department of Food Science and Chemical Technology, University of Chile, Santiago, Chile.
authors.forename: Nalda
authors.initials: N
authors.lastname: Romero
authors.affiliation: Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez
authors.affiliation: Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruz
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose / Q000032:analysis; D059305:Diet, High-Fat / Q000009:adverse effects*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage; D005215:Fasting; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008066:Lipolysis; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000517:prevention & control*; D000069463:Olive Oil / Q000008:administration & dosage*; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D007328:Insulin; D015850:Interleukin-6; D000069463:Olive Oil; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid