title: Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms.
abstract: The thyroid hormones (THs) 3,3',5,5'-tetraiodo-l-thyronine (T4) and 3,5,3'-triiodo-l-thyronine (T3) influence many metabolic pathways. The major physiological function of THs is to sustain basal energy expenditure, by acting primarily on carbohydrate and lipid catabolism. Beyond the mobilization and degradation of lipids, at the hepatic level THs stimulate the de novo fatty acid synthesis (de novo lipogenesis, DNL), through both the modulation of gene expression and the rapid activation of cell signalling pathways. 3,5-Diiodo-l-thyronine (T2), previously considered only a T3 catabolite, has been shown to mimic some of T3 effects on lipid catabolism. However, T2 action is more rapid than that of T3, and seems to be independent of protein synthesis. An inhibitory effect on DNL has been documented for T2. Here, we give an overview of the mechanisms of THs action on liver fatty acid metabolism, focusing on the different effects exerted by T2 and T3 on the regulation of the DNL. The inhibitory action on DNL exerted by T2 makes this compound a potential and attractive drug for the treatment of some metabolic diseases and cancer.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy. fabrizio.damiano@unisalento.it.
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, 73100 Lecce, Italy. alessio.rochira@unisalento.it.
authors.forename: Alessio
authors.initials: A
authors.lastname: Rochira
authors.affiliation: Department of Basic Medical Sciences, Section of Medical Biochemistry, University of Bari Aldo Moro, 70125 Bari, Italy. Antonio.gnoni@uniba.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gnoni
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy. luisa.siculella@unisalento.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Siculella
mesh_terms: D000818:Animals; D004104:Diiodothyronines / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D004104:Diiodothyronines; D005227:Fatty Acids; D014284:Triiodothyronine; C030103:3,5-diiodothyronine; D013974:Thyroxine
keywords: 3,5,3′-triiodo-l-thyronine; 3,5-diiodo-l-thyronine; acetyl-CoA carboxylase; citrate carrier; de novo lipogenesis; fatty acid synthase; lipid lowering action