Review
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World J Hepatol. Mar 27, 2014; 6(3): 114-129
Published online Mar 27, 2014. doi: 10.4254/wjh.v6.i3.114
Thyroid hormone analogues and derivatives: Actions in fatty liver
Maria Coppola, Daniela Glinni, Maria Moreno, Federica Cioffi, Elena Silvestri, Fernando Goglia
Maria Coppola, Daniela Glinni, Maria Moreno, Federica Cioffi, Elena Silvestri, Fernando Goglia, Department of Science and Technologies, University of Sannio, 82100 Benevento, Italy
Author contributions: Coppola M and Glinni D contributed equally to this work; Coppola M wrote the paragraph: Naturally occurring iodothyronines and liver steatosis: 3,5-T2; Glinni D wrote the paragraph: Actions of T3 on lipid metabolism in the liver: implications for fatty liver; Moreno M wrote the paragraphs: Introduction and Conclusions; Cioffi F wrote the paragraph: Thyroid hormone functional analogues: TRC150094 (TRC); Silvestri E wrote the paragraph: Thyromimetics and liver steatosis and realized the figures; Goglia F coordinated all the work and revised all the manuscript.
Correspondence to: Fernando Goglia, Professor of Physiology, Head of Department of Science and Technologies, University of Sannio, Via Port’Arsa 11, 82100 Benevento, Italy. goglia@unisannio.it
Telephone: +39-0824-305100 Fax: +39-0824-305142
Received: October 30, 2013
Revised: December 10, 2013
Accepted: February 16, 2014
Published online: March 27, 2014
Processing time: 140 Days and 0.7 Hours
Abstract

Fatty liver or nonalcoholic fatty liver disease (NAFLD), a problem of increasing clinical significance and prevalence worldwide, is associated with increased risk for the development of cirrhosis and hepatocellular carcinoma. Although several therapeutic approaches can be used in the context of NAFLD, dietary and physical activities are still the most frequently used strategies. Some pharmacological agents show promising results although no conclusions can be drawn from recent clinical trials. Thyroid hormones [THs; thyroxine (T4) and 3,3′,5-triiodo-L-thyronine (T3)] coordinate a diverse array of physiological events during development and lipid/energy homeostasis and have some potentially therapeutic actions which include inducing weight loss, and lowering plasma cholesterol levels and tissue adiposity. The thyroid hormones exert their physiological effects by binding to specific nuclear receptors [thyroid hormone receptors (TR)] of which the TRβ isoform is liver specific and has been considered a putative target for the treatment of dyslipidemia and fatty liver. In view of this, the aim of the review is (1) to provide an overview of the action of T3 on lipid metabolism with implications for liver steatosis and (2) to provide an update on the current knowledge concerning the administration of TRβ selective thyromimetics (GC-1 and MB07811), as well as of 3,5-diiodo-L-thyronine and its novel functional analogue TRC150094 in animal models of overweight and related disorders including primarily fatty liver.

Keywords: Fatty liver; Thyroid hormones; Thyromimetics; 3,5-diiodo-L-thyronine; Lipid metabolism

Core tip: Fatty liver is associated with increased risk for the development of cirrhosis and hepatocellular carcinoma. Thyroid hormones have some potentially therapeutic actions by binding to specific nuclear receptors [thyroid hormone receptors (TR)] of which the TRβ isoform is liver specific and a putative target for the treatment of dyslipidemia and fatty liver. This review provides (1) an overview of the action of T3 on lipid metabolism and (2) an update concerning the administration of TRβ selective thyromimetics (GC-1 and MB07811), as well as of 3,5-diiodo-L-thyronine and its novel functional analogue TRC150094 in animal models of overweight and fatty liver.