AIM:To investigate the redox dependency and promotion of downstream targets in thyroid hormone(T3)-induced AMP-activated protein kinase(AMPK)signaling as cellular energy sensor to limit metabolic stresses in the liver.METHODS:Fed male Sprague-Dawley rats were given a single ip dose of 0.1 mg T3/kg or T3 vehicle(Na OH0.1 N;controls)and studied at 8 or 24 h after treatment.Separate groups of animals received 500 mg N-acetylcysteine(NAC)/kg or saline ip 30 min prior T3.Measurements included plasma and liver 8-isoprostane and serumβ-hydroxybutyrate levels(ELISA),hepaticlevels of m RNAs(q PCR),proteins(Western blot),and phosphorylated AMPK(ELISA).RESULTS:T3 upregulates AMPK signaling,including the upstream kinases Ca2+-calmodulin-dependent protein kinase kinase-βand transforming growth factor-β-activated kinase-1,with T3-induced reactive oxygen species having a causal role due to its suppression by pretreatment with the antioxidant NAC.Accordingly,AMPK targets acetyl-Co A carboxylase and cyclic AMP response element binding protein are phosphorylated,with the concomitant carnitine palmitoyltransferase-1α(CPT-1α)activation and higher expression of peroxisome proliferator-activated receptor-γco-activator-1αand that of the fatty acid oxidation(FAO)-related enzymes CPT-1α,acyl-Co A oxidase 1,and acylCo A thioesterase 2.Under these conditions,T3 induced a significant increase in the serum levels ofβ-hydroxybutyrate,a surrogate marker for hepatic FAO.CONCLUSION:T3 administration activates liver AMPK signaling in a redox-dependent manner,leading to FAO enhancement as evidenced by the consequent ketogenic response,which may constitute a key molecular mechanism regulating energy dynamics to support T3preconditioning against ischemia-reperfusion injury. AIM: To investigate the redox dependency and promotion of hypobic targets in thyroid hormone (T3) -induced AMP-activated protein kinase (AMPK) signaling as cellular energy sensor to limit metabolic stresses in the liver. METHODS: Fed male Sprague-Dawley rats were given a single ip dose of 0.1 mg T3 / kg or T3 vehicle (Na OH 0.1 N; controls) and studied at 8 or 24 h after treatment. Separate groups of animals received 500 mg N-acetylcysteine ​​(NAC) / kg or saline ip 30 min prior T3.Measurements included plasma and liver 8-isoprostane and serum β-hydroxybutyrate levels (ELISA), hepaticlevels of m RNAs (q PCR), proteins (Western blot), and phosphorylated AMPK signaling, including the upstream kinases Ca2 + -calmodulin-dependent protein kinase kinase-β and transforming growth factor-β-activated kinase-1, with T3-induced reactive oxygen species having a causal role due to its suppression by pretreatment with the antioxidant NAC. Accredited , AMPK targets acetyl-Co A carboxylase and cyclic AMP response element binding protein are phosphorylated with the concomitant carnitine palmitoyltransferase-1α (CPT-1α) activation and higher expression of peroxisome proliferator-activated receptor-γco-activator-1αand that of the fatty acid oxidation (FAO) -lated enzymes CPT -1α, acyl-Co A oxidase 1, and acylCo A thioesterase 2. Undersen these conditions, T3 induced a significant increase in the serum levels of β-hydroxybutyrate, a surrogate marker for hepatic FAO.CONCLUSION: T3 administration activates liver AMPK signaling in a redox-dependent manner, leading to FAO enhancement as evidenced by the consequent ketogenic response, which may constitute a key molecular mechanism regulating energy dynamics to support T3 preconditioning against ischemia-reperfusion injury.