PMID- 30578580
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20190722
IS  - 1872-8081 (Electronic)
IS  - 0951-6433 (Linking)
VI  - 45
IP  - 2
DP  - 2019 Mar
TI  - Docosahexaenoic acid-thyroid hormone combined protocol as a novel approach to 
      metabolic stress disorders: Relation to mitochondrial adaptation via liver PGC-1alpha 
      and sirtuin1 activation.
PG  - 271-278
LID - 10.1002/biof.1483 [doi]
AB  - Docosahexaenoic acid (DHA) and 3,3',5-triiodothyronine (T(3) ) 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 + T(3) 
      accomplish mitochondrial adaptation through downstream upregulation of PPAR-gamma 
      coactivator 1alpha (PGC-1alpha). 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 T(3) /kg (or hormone vehicle) ip at the fourth day, or single dose of 0.1 mg 
      T(3) /kg alone. Liver mRNA levels were assayed by qPCR, NAD(+) /NADH ratios, 
      hepatic proteins, histone 3 acetylation and serum T(3) and beta-hydroxybutyrate 
      levels were determined by specific ELISA kits. Combined DHA + T(3) protocol led 
      to increased liver AMPK, PGC-1alpha, NRF-2, COX-IV, and beta-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 beta-hydroxybutyrate over control values. These changes were 
      reproduced by the higher dose of T(3) without major alterations by DHA or T(3) 
      alone. In conclusion, liver mitochondrial adaptation by DHA + T(3) is associated 
      with PGC-1alpha upregulation involving enhanced transcription of the coactivator, 
      which may be contributed by PGC-1alpha deacetylation and phosphorylation by SIRT1 and 
      AMPK activation, respectively. This contention is supported by NRF-2-dependent 
      enhancement in COX-1 and beta-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. (c) 2018 
      BioFactors, 45(2):271-278, 2019.
CI  - (c) 2018 International Union of Biochemistry and Molecular Biology.
FAU - Vargas, Romina
AU  - Vargas R
AD  - Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, 
      Faculty of Medicine, University of Chile, Santiago, Chile.
FAU - Riquelme, Barbara
AU  - Riquelme B
AD  - Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, 
      Faculty of Medicine, University of Chile, Santiago, Chile.
FAU - Fernandez, Javier
AU  - Fernandez J
AD  - Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, 
      Faculty of Medicine, University of Chile, Santiago, Chile.
FAU - Alvarez, Daniela
AU  - Alvarez D
AD  - Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, 
      Faculty of Medicine, University of Chile, Santiago, Chile.
FAU - Perez, Ignacio F
AU  - Perez IF
AD  - Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, 
      Faculty of Medicine, University of Chile, Santiago, Chile.
FAU - Cornejo, Pamela
AU  - Cornejo P
AD  - Health and Odontology Faculty, Diego Portales University, Santiago, Chile.
FAU - Fernandez, Virginia
AU  - Fernandez V
AD  - Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, 
      Faculty of Medicine, University of Chile, Santiago, Chile.
FAU - Videla, Luis A
AU  - Videla LA
AUID- ORCID: 0000-0002-1788-6667
AD  - Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, 
      Faculty of Medicine, University of Chile, Santiago, Chile.
LA  - eng
GR  - 1150104/National Fund for Scientific & Technological Development (FONDECYT, 
      Chile)/
PT  - Journal Article
DEP - 20181221
PL  - Netherlands
TA  - Biofactors
JT  - BioFactors (Oxford, England)
JID - 8807441
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Thyroid Hormones)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Docosahexaenoic Acids/*pharmacology
MH  - Liver/*drug effects/*metabolism
MH  - Male
MH  - Mitochondria/drug effects/*metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/*metabolism
MH  - Stress, Physiological
MH  - Thyroid Hormones/*pharmacology
OTO - NOTNLM
OT  - PGC-1alpha
OT  - SIRT1
OT  - docosahexaenoic acid
OT  - ketogenic response
OT  - liver
OT  - thyroid hormone
EDAT- 2018/12/24 06:00
MHDA- 2019/07/23 06:00
CRDT- 2018/12/23 06:00
PHST- 2018/10/22 00:00 [received]
PHST- 2018/11/20 00:00 [revised]
PHST- 2018/11/26 00:00 [accepted]
PHST- 2018/12/24 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2018/12/23 06:00 [entrez]
AID - 10.1002/biof.1483 [doi]
PST - ppublish
SO  - Biofactors. 2019 Mar;45(2):271-278. doi: 10.1002/biof.1483. Epub 2018 Dec 21.