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

Abstract

© 2018 International Union of Biochemistry and Molecular Biology 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-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 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 β-hydroxybutyrate levels were determined by specific ELISA kits. Combined DHA + T 3 protocol led to increased liver AMPK, PGC-1α, NRF-2, COX-IV, and β-ATP synthase mRNAs, with concomitant higher protein levels of COX-IV and NRF-2, 369% enhancement