title: Acute administration of 3,5-diiodo-L-thyronine to hypothyroid rats stimulates bioenergetic parameters in liver mitochondria.
abstract: The role of 3,5-diiodo-L-thyronine (T2), initially considered only a 3,3',5-triiodo-L-thyronine (T3) catabolite, in the bioenergetic metabolism is of growing interest. In this study we investigated the acute effects (within 1 h) of T2administration to hypothyroid rats on liver mitochondria fatty acid uptake and β-oxidation rate, mitochondrial efficiency (by measuring proton leak) and mitochondrial oxidative damage (by determining H2O2release). Fatty acid uptake into mitochondria was measured assaying carnitine palmitoyl transferase (CPT) I and II activities, and fatty acid β-oxidation using palmitoyl-CoA as a respiratory substrate. Mitochondrial fatty acid pattern was defined by gas-liquid chromatography. In hypothyroid + T2vs hypothyroid rats we observed a raise in the serum level of nonesterified fatty acids (NEFA), in the mitochondrial CPT system activity and in the fatty acid β-oxidation rate. A parallel increase in the respiratory chain activity, mainly from succinate, occurs. When fatty acids are chelated by bovine serum albumin, a T2-induced increase in both state 3 and state 4 respiration is observed, while, when fatty acids are present, mitochondrial uncoupling occurs together with increased proton leak, responsible for mitochondrial thermogenesis. T2administration decreases mitochondrial oxidative stress as determined by lower H2O2production. We conclude that in rat liver mitochondria T2acutely enhances the rate of fatty acid β-oxidation, and the activity of the downstream respiratory chain. The T2-induced increase in proton leak may contribute to mitochondrial thermogenesis and to the reduction of oxidative stress. Our results strengthen the previously reported ability of T2to reduce adiposity, dyslipidemia and to prevent liver steatosis.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, 73100, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cavallo
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, 73100, Italy.|Center of Integrated Research, Campus Bio-Medico, University of Rome, Rome, 00100, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Taurino
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, 73100, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Damiano
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, 73100, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Siculella
authors.affiliation: Center of Integrated Research, Campus Bio-Medico, University of Rome, Rome, 00100, Italy.|Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Policlinico P.zza G. Cesare 11, Bari, 70100, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sardanelli
authors.affiliation: Center of Integrated Research, Campus Bio-Medico, University of Rome, Rome, 00100, Italy. antonio.gnoni@uniba.it.|Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Policlinico P.zza G. Cesare 11, Bari, 70100, Italy. antonio.gnoni@uniba.it.|Center for Biomolecular Nanotechnologies (CBN), Via Barsanti 14, Arnesano (Lecce), 73010, Italy. antonio.gnoni@uniba.it.|Istituto Italiano di Tecnologia, Arnesano (Lecce), 73010, Italy. antonio.gnoni@uniba.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gnoni
mesh_terms: D000818:Animals; D004104:Diiodothyronines / Q000008:administration & dosage / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D007037:Hypothyroidism / Q000188:drug therapy*; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004104:Diiodothyronines; D005227:Fatty Acids; D014475:Uncoupling Agents; C030103:3,5-diiodothyronine
keywords: 3,5-diiodo-L-thyronine; Lipid composition; Mitochondrial fatty acid uptake and oxidation; Oxidative stress; Proton leak; Respiratory chain