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Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice.
Lipids Health Dis 2017; 16(1):64LH

Abstract

BACKGROUND

Eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) are long-chain polyunsaturated fatty acids (LCPUFAs) with relevant roles in the organism. EPA and DHA are synthesized from the precursor alpha-linolenic acid (ALA, C18:3n-3), whereas AA is produced from linoleic acid (LA, C18:2n-6) through the action of Δ5 and Δ6-desaturases. High-fat diet (HFD) decreases the activity of both desaturases and LCPUFA accretion in liver and other tissues. Hydroxytyrosol (HT), a natural antioxidant, has an important cytoprotective effects in different cells and tissues.

METHODS

Male mice C57BL/6 J were fed a control diet (CD) (10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks. Animals were daily supplemented with saline (CD) or 5 mg HT (HFD), and blood and the studied tissues were analyzed after the HT intervention. Parameters studied included liver histology (optical microscopy), activity of hepatic desaturases 5 and 6 (gas-liquid chromatography of methyl esters derivatives) and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by spectrophotometry), oxidative stress indicators (glutathione, thiobarbituric acid reactants, and the antioxidant capacity of plasma), gene expression assays for sterol regulatory element-binding protein 1c (SREBP-1c) (qPCR and ELISA), and LCPUFA profiles in liver, erythrocyte, brain, heart, and testicle (gas-liquid chromatography).

RESULTS

HFD led to insulin resistance and liver steatosis associated with SREBP-1c upregulation, with enhancement in plasma and liver oxidative stress status and diminution in the synthesis and storage of n-6 and n-3 LCPUFAs in the studied tissues, compared to animals given control diet. HT supplementation significantly reduced fat accumulation in liver and plasma as well as tissue metabolic alterations induced by HFD. Furthermore, a normalization of desaturase activities, oxidative stress-related parameters, and tissue n-3 LCPUFA content was observed in HT-treated rats over control animals.

CONCLUSIONS

HT supplementation prevents metabolic alterations in desaturase activities, oxidative stress status, and n-3 LCPUFA content in the liver and extrahepatic tissues of mice fed HFD.

Authors+Show Affiliations

Nutrition Department, Faculty of Medicine, University of Chile, Independencia 1027, Casilla, 70000, Santiago 7, Chile. rvalenzuelab@med.uchile.cl. Lipid Center, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile. rvalenzuelab@med.uchile.cl.Nutrition Department, Faculty of Medicine, University of Chile, Independencia 1027, Casilla, 70000, Santiago 7, Chile.Nutrition Department, Faculty of Medicine, University of Chile, Independencia 1027, Casilla, 70000, Santiago 7, Chile.Lipid Center, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile.Medical Technology Department, Faculty of Medicine, University of Chile, Santiago, Chile.Nutrition Department, Faculty of Medicine, University of Chile, Independencia 1027, Casilla, 70000, Santiago 7, Chile.Biochemistry Department. Faculty of Biochemistry, University of Litoral, Santa Fe, Argentina.Lipid Center, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, 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

28395666

Citation

Valenzuela, Rodrigo, et al. "Hydroxytyrosol Prevents Reduction in Liver Activity of Δ-5 and Δ-6 Desaturases, Oxidative Stress, and Depletion in Long Chain Polyunsaturated Fatty Acid Content in Different Tissues of High-fat Diet Fed Mice." Lipids in Health and Disease, vol. 16, no. 1, 2017, p. 64.
Valenzuela R, Echeverria F, Ortiz M, et al. Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice. Lipids Health Dis. 2017;16(1):64.
Valenzuela, R., Echeverria, F., Ortiz, M., Rincón-Cervera, M. Á., Espinosa, A., Hernandez-Rodas, M. C., ... Videla, L. A. (2017). Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice. Lipids in Health and Disease, 16(1), p. 64. doi:10.1186/s12944-017-0450-5.
Valenzuela R, et al. Hydroxytyrosol Prevents Reduction in Liver Activity of Δ-5 and Δ-6 Desaturases, Oxidative Stress, and Depletion in Long Chain Polyunsaturated Fatty Acid Content in Different Tissues of High-fat Diet Fed Mice. Lipids Health Dis. 2017 Apr 11;16(1):64. PubMed PMID: 28395666.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice. AU - Valenzuela,Rodrigo, AU - Echeverria,Francisca, AU - Ortiz,Macarena, AU - Rincón-Cervera,Miguel Ángel, AU - Espinosa,Alejandra, AU - Hernandez-Rodas,María Catalina, AU - Illesca,Paola, AU - Valenzuela,Alfonso, AU - Videla,Luis A, Y1 - 2017/04/11/ PY - 2017/01/22/received PY - 2017/03/09/accepted PY - 2017/4/12/entrez PY - 2017/4/12/pubmed PY - 2017/7/27/medline KW - Antioxidant capacity KW - Hydroxytyrosol KW - LCPUFA KW - Liver and extrahepatic tissues KW - Oxidative stress KW - Δ5/Δ6 Desaturase activity SP - 64 EP - 64 JF - Lipids in health and disease JO - Lipids Health Dis VL - 16 IS - 1 N2 - BACKGROUND: Eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) are long-chain polyunsaturated fatty acids (LCPUFAs) with relevant roles in the organism. EPA and DHA are synthesized from the precursor alpha-linolenic acid (ALA, C18:3n-3), whereas AA is produced from linoleic acid (LA, C18:2n-6) through the action of Δ5 and Δ6-desaturases. High-fat diet (HFD) decreases the activity of both desaturases and LCPUFA accretion in liver and other tissues. Hydroxytyrosol (HT), a natural antioxidant, has an important cytoprotective effects in different cells and tissues. METHODS: Male mice C57BL/6 J were fed a control diet (CD) (10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks. Animals were daily supplemented with saline (CD) or 5 mg HT (HFD), and blood and the studied tissues were analyzed after the HT intervention. Parameters studied included liver histology (optical microscopy), activity of hepatic desaturases 5 and 6 (gas-liquid chromatography of methyl esters derivatives) and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by spectrophotometry), oxidative stress indicators (glutathione, thiobarbituric acid reactants, and the antioxidant capacity of plasma), gene expression assays for sterol regulatory element-binding protein 1c (SREBP-1c) (qPCR and ELISA), and LCPUFA profiles in liver, erythrocyte, brain, heart, and testicle (gas-liquid chromatography). RESULTS: HFD led to insulin resistance and liver steatosis associated with SREBP-1c upregulation, with enhancement in plasma and liver oxidative stress status and diminution in the synthesis and storage of n-6 and n-3 LCPUFAs in the studied tissues, compared to animals given control diet. HT supplementation significantly reduced fat accumulation in liver and plasma as well as tissue metabolic alterations induced by HFD. Furthermore, a normalization of desaturase activities, oxidative stress-related parameters, and tissue n-3 LCPUFA content was observed in HT-treated rats over control animals. CONCLUSIONS: HT supplementation prevents metabolic alterations in desaturase activities, oxidative stress status, and n-3 LCPUFA content in the liver and extrahepatic tissues of mice fed HFD. SN - 1476-511X UR - https://www.unboundmedicine.com/medline/citation/28395666/Hydroxytyrosol_prevents_reduction_in_liver_activity_of_Δ_5_and_Δ_6_desaturases_oxidative_stress_and_depletion_in_long_chain_polyunsaturated_fatty_acid_content_in_different_tissues_of_high_fat_diet_fed_mice_ L2 - https://lipidworld.biomedcentral.com/articles/10.1186/s12944-017-0450-5 DB - PRIME DP - Unbound Medicine ER -