Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms - PubMed (original) (raw)
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Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms
Fabrizio Damiano et al. Int J Mol Sci. 2017.
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.
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.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Figure 1
(A) Schematic representation of the role of T3 in the stimulation of activity and expression of enzymes, mitochondrial carriers, and transcription factors involved in the synthesis of palmitic acid from glucose; and (B) Effects of T3 on the activation of fatty acid synthesis through thyroid receptors (TRs) and lipogenic transcription factors (SREBP-1 and ChREBP). Abbreviations: ACC, Acetyl-CoA carboxylase; ACLY, ATP-citrate lyase; ChREBP, Carbohydrate Response Element Binding Protein; CiC, Citrate carrier; DNL, De novo lipogenesis; FAS, Fatty acid synthase; G6PD, Glucose-6-phosphate dehydrogenase; L-PK, Liver pyruvate kinase; MPC, Mitochondrial pyruvate carrier; ME, Malic enzyme; OAA; oxalacetic acid; SREBP-1, Sterol regulatory element-binding protein 1; TCA, Tricarboxylic acid cycle.
Figure 2
Scheme of the inhibition of fatty acid synthesis mediated by T2. Green line-arrow, Stimulation; Red T-bar, Inhibition; Red cross, Loss of stimulation/inhibition consequent to T2 action. Abbreviations: ACC, Acetyl-CoA carboxylase; AMPK, AMP-activated protein kinase; CPTI, Carnitine palmitoyltransferase I; FAS, Fatty acid synthase; nSREBP-1, nuclear sterol regulatory element-binding protein 1; pSREBP-1, precursor sterol regulatory element-binding protein 1; SIRT1, Sirtuin 1.
References
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