T3-induced liver AMP-activated protein kinase signaling: Redox dependency and upregulation of downstream targets

Figure 1 Effect of N-acetylcysteine on T₃-induced liver CaMKKβ/TAK1-AMPK cascade. (A) Rat plasma and liver 8-isoprostane levels, liver mRNA levels of AMPK (B) and CaMKKβ (C, E) hepatic CaMKKβ protein content, and liver expression of TAK1 mRNA (D) and pTAK1/TAK1 ratios (F). Values shown are means ± SEM (n = 3-4). Statistical significance (one-way ANOVA and the Newman-Keuls, test; P < 0.05) is indicated by the letters identifying each experimental group. AMPK: AMP-activated protein kinase; CaMKKβ: Ca²⁺-calmodulin-dependent protein kinase kinase-β; NAC: N-acetylcysteine; (p)TAK1, (phosphorylated) transforming growth factor-β-activated kinase-1.

Figure 2 T₃-induced changes in liver direct AMP-activated protein kinase targets. A: pAMPK levels; B: PGC-1α mRNA content; C: Contents of ACC-α mRNA and pACC-α; D: Levels of CREB mRNA and pCREB/CREB ratios; E: Correlations between pAMPK and pACC-α, pCREB/CREB ratios, and PGC-1α. Values shown are means ± SEM (n = 3-6). Statistical significance was performed by one-way ANOVA and the Newman-Keuls, test (C, D) or Student,s t-test for unpaired data (A, B) (P < 0.05). Associations between variables were analyzed by the Pearson correlation coefficient. pAMPK: Phosphorylated AMP-activated protein kinase; (p) ACC-α: (Phosphorylated) acetyl-CoA carboxylase-α; (p)CREB: (phosphorylated) cAMP-response element-binding protein; PGC-1α: Peroxisome proliferator-activated receptor-γ coactivator-1α.

Figure 3 T₃-induced changes in liver AMPK-dependent targets related to fatty acid oxidation. mRNA and protein levels of CPT-1α (A), ACOX1 (B), and ACOT2 (C), and circulating levels of β-hydroxybutyrate (D). Values shown are means ± SEM (n = 3-5). Statistical significance was performed by Student,s t-test for unpaired data (P < 0.05). AMPK: AMP-activated protein kinase; ACOT2: Acyl-CoA thioesterase 2; ACOX1: Acyl-CoA oxidase 1; CPT-1α: Carnitine palmitolytransferase-1α.

Figure 4 Schematic representation of T₃ signaling related to AMPK upregulation and consequent fatty acid oxidation enhancement. ACC: Acetyl-CoA carboxylase; ACOT2: acyl-CoA thioesterase 2; ACOX1: acyl-CoA oxidase 1; AMPK: AMP-activated protein kinase; CaMKKβ: Ca²⁺-calmodulin-dependent protein kinase kinase-β; CBP/p300: CREB-binding protein; CPT-1α: Carnitine palmitolytransferase-1α; CREB: cAMP-response element-binding protein; FA: Fatty acid; PGT-1α: Peroxisome proliferator-activated receptor-γ coactivator-1α; QO₂: Rate of oxygen consumption; ROS: Reactive oxygen species; TAK1: Transforming growth factor-β-activated kinase-1.