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Docosahexaenoic acid-thyroid hormone combined protocol as a novel approach to metabolic stress disorders: Relation to mitochondrial adaptation via liver PGC-1α and sirtuin1 activation.
Vargas, Romina; Riquelme, Bárbara; Fernández, Javier; Álvarez, Daniela; Pérez, Ignacio F; Cornejo, Pamela; Fernández, Virginia; Videla, Luis A.
Afiliação
  • Vargas R; Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Riquelme B; Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Fernández J; Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Álvarez D; Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Pérez IF; Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Cornejo P; Health and Odontology Faculty, Diego Portales University, Santiago, Chile.
  • Fernández V; Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
  • Videla LA; Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Biofactors ; 45(2): 271-278, 2019 Mar.
Article em En | MEDLINE | ID: mdl-30578580
Docosahexaenoic acid (DHA) and 3,3',5-triiodothyronine (T3 ) combined protocol affords protection against liver injury via AMPK signaling supporting energy requirements. The aim of this work was to test the hypothesis that a DHA + T3 accomplish mitochondrial adaptation through downstream upregulation of PPAR-γ coactivator 1α (PGC-1α). Male Sprague-Dawley rats were given daily oral doses of 300 mg DHA/kg or saline (controls) for three consecutive days, followed by 0.05 mg T3 /kg (or hormone vehicle) ip at the fourth day, or single dose of 0.1 mg T3 /kg alone. Liver mRNA levels were assayed by qPCR, NAD+ /NADH ratios, hepatic proteins, histone 3 acetylation and serum T3 and ß-hydroxybutyrate levels were determined by specific ELISA kits. Combined DHA + T3 protocol led to increased liver AMPK, PGC-1α, NRF-2, COX-IV, and ß-ATP synthase mRNAs, with concomitant higher protein levels of COX-IV and NRF-2, 369% enhancement in the NAD+ /NADH ratio, 47% decrease in histone 3 acetylation and 162% increase in serum levels of ß-hydroxybutyrate over control values. These changes were reproduced by the higher dose of T3 without major alterations by DHA or T3 alone. In conclusion, liver mitochondrial adaptation by DHA + T3 is associated with PGC-1α upregulation involving enhanced transcription of the coactivator, which may be contributed by PGC-1α deacetylation and phosphorylation by SIRT1 and AMPK activation, respectively. This contention is supported by NRF-2-dependent enhancement in COX-1 and ß-ATP synthase induction with higher fatty acid oxidation resulting in a significant ketogenic response, which may represent a suitable strategy for hepatic steatosis with future clinical applications. © 2018 BioFactors, 45(2):271-278, 2019.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hormônios Tireóideos / Ácidos Docosa-Hexaenoicos / Sirtuína 1 / Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo / Fígado / Mitocôndrias Tipo de estudo: Guideline Limite: Animals Idioma: En Revista: Biofactors Assunto da revista: BIOQUIMICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Chile

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hormônios Tireóideos / Ácidos Docosa-Hexaenoicos / Sirtuína 1 / Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo / Fígado / Mitocôndrias Tipo de estudo: Guideline Limite: Animals Idioma: En Revista: Biofactors Assunto da revista: BIOQUIMICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Chile