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High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism: attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration.
Food Funct. 2019 Sep 01; 10(9):6170-6183.FF

Abstract

High-fat-diet (HFD) feeding is associated with liver oxidative stress (OS), n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) depletion, hepatic steatosis and mitochondrial dysfunction. Our hypothesis is that the HFD-induced liver injury can be attenuated by the combined supplementation of n-3 LCPUFA eicosapentaenoic acid (EPA) and the antioxidant hydroxytyrosol (HT). The C57BL/6J mice were administered an HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg kg-1 day-1), HT (5 mg kg-1 day-1), or EPA + HT (50 and 5 mg kg-1 day-1, respectively) for 12 weeks. We measured the body and liver weights and dietary and energy intakes along with liver histology, FA composition, steatosis score and associated transcription factors, mitochondrial functions and metabolic factors related to energy sensing through the AMP-activated protein kinase (AMPK) and PPAR-γ coactivator-1α (PGC-1α) cascade. It was found that the HFD significantly induced liver steatosis, with a 66% depletion of n-3 LCPUFAs and a 100% increase in n-6/n-3 LCPUFA ratio as compared to the case of CD (p < 0.05). These changes were concomitant with (i) a 95% higher lipogenic and 70% lower FA oxidation signaling, (ii) a 40% diminution in mitochondrial respiratory capacity and (iii) a 56% lower ATP content. HFD-induced liver steatosis was also associated with (iv) a depressed mRNA expression of AMPK-PGC-1α signaling components, nuclear respiratory factor-2 (NRF-2) and β-ATP synthase. These HFD effects were significantly attenuated by the combined EPA + HT supplementation in an additive manner. These results suggested that EPA and HT co-administration partly prevented HFD-induced liver steatosis, thus strengthening the importance of combined interventions in hepatoprotection in non-alcoholic fatty liver disease.

Authors+Show Affiliations

Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.Nutrition Department, Faculty of Medicine, University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.Nutrition and Dietetics School, Faculty of Health Sciences, Catholic University of Maule, Curicó, Chile.Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago, Chile.Biochemistry Department, Faculty of Biochemistry, University of Litoral, Santa Fe, Argentina.Núcleo de Química y Bioquímica, Facultad de Ciencias, Universidad Mayor, Chile.Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, University of Chile, Santiago, Chile.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31501836

Citation

Echeverría, Francisca, et al. "High-fat Diet Induces Mouse Liver Steatosis With a Concomitant Decline in Energy Metabolism: Attenuation By Eicosapentaenoic Acid (EPA) or Hydroxytyrosol (HT) Supplementation and the Additive Effects Upon EPA and HT Co-administration." Food & Function, vol. 10, no. 9, 2019, pp. 6170-6183.
Echeverría F, Valenzuela R, Bustamante A, et al. High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism: attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration. Food Funct. 2019;10(9):6170-6183.
Echeverría, F., Valenzuela, R., Bustamante, A., Álvarez, D., Ortiz, M., Espinosa, A., Illesca, P., Gonzalez-Mañan, D., & Videla, L. A. (2019). High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism: attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration. Food & Function, 10(9), 6170-6183. https://doi.org/10.1039/c9fo01373c
Echeverría F, et al. High-fat Diet Induces Mouse Liver Steatosis With a Concomitant Decline in Energy Metabolism: Attenuation By Eicosapentaenoic Acid (EPA) or Hydroxytyrosol (HT) Supplementation and the Additive Effects Upon EPA and HT Co-administration. Food Funct. 2019 Sep 1;10(9):6170-6183. PubMed PMID: 31501836.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism: attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration. AU - Echeverría,Francisca, AU - Valenzuela,Rodrigo, AU - Bustamante,Andrés, AU - Álvarez,Daniela, AU - Ortiz,Macarena, AU - Espinosa,Alejandra, AU - Illesca,Paola, AU - Gonzalez-Mañan,Daniel, AU - Videla,Luis A, Y1 - 2019/09/10/ PY - 2019/9/11/pubmed PY - 2020/2/12/medline PY - 2019/9/11/entrez SP - 6170 EP - 6183 JF - Food & function JO - Food Funct VL - 10 IS - 9 N2 - High-fat-diet (HFD) feeding is associated with liver oxidative stress (OS), n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) depletion, hepatic steatosis and mitochondrial dysfunction. Our hypothesis is that the HFD-induced liver injury can be attenuated by the combined supplementation of n-3 LCPUFA eicosapentaenoic acid (EPA) and the antioxidant hydroxytyrosol (HT). The C57BL/6J mice were administered an HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg kg-1 day-1), HT (5 mg kg-1 day-1), or EPA + HT (50 and 5 mg kg-1 day-1, respectively) for 12 weeks. We measured the body and liver weights and dietary and energy intakes along with liver histology, FA composition, steatosis score and associated transcription factors, mitochondrial functions and metabolic factors related to energy sensing through the AMP-activated protein kinase (AMPK) and PPAR-γ coactivator-1α (PGC-1α) cascade. It was found that the HFD significantly induced liver steatosis, with a 66% depletion of n-3 LCPUFAs and a 100% increase in n-6/n-3 LCPUFA ratio as compared to the case of CD (p < 0.05). These changes were concomitant with (i) a 95% higher lipogenic and 70% lower FA oxidation signaling, (ii) a 40% diminution in mitochondrial respiratory capacity and (iii) a 56% lower ATP content. HFD-induced liver steatosis was also associated with (iv) a depressed mRNA expression of AMPK-PGC-1α signaling components, nuclear respiratory factor-2 (NRF-2) and β-ATP synthase. These HFD effects were significantly attenuated by the combined EPA + HT supplementation in an additive manner. These results suggested that EPA and HT co-administration partly prevented HFD-induced liver steatosis, thus strengthening the importance of combined interventions in hepatoprotection in non-alcoholic fatty liver disease. SN - 2042-650X UR - https://www.unboundmedicine.com/medline/citation/31501836/High_fat_diet_induces_mouse_liver_steatosis_with_a_concomitant_decline_in_energy_metabolism:_attenuation_by_eicosapentaenoic_acid__EPA__or_hydroxytyrosol__HT__supplementation_and_the_additive_effects_upon_EPA_and_HT_co_administration_ L2 - https://doi.org/10.1039/c9fo01373c DB - PRIME DP - Unbound Medicine ER -