Lipid lowering effects of iodothyronines: In vivo and in vitro studies on rat liver - PubMed (original) (raw)

Review

Lipid lowering effects of iodothyronines: In vivo and in vitro studies on rat liver

Laura Vergani. World J Hepatol. 2014.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common liver diseases, leading to the increasing interest for new therapeutic approaches for its treatment. NAFLD primarily depends on a hypercaloric and/or unbalanced diet leading to overweight and obesity. The liver, in fact, plays a central role in lipid metabolism by importing free fatty acids from the blood and synthesizing, storing, oxidizing and exporting lipids. Furthermore, the liver is the target for the thyroid hormones, thyroxine (T4) and 3,3',5-triiodo-L-thyronine (T3), that stimulate the basal metabolic rate and lead to body weight loss. In the last decade, other iodothyronines have been shown to possess biological relevance and play some thyromimetic activities; in particular, 3,5-diiodo-L-thyronine (T2) gained large interest. The global effect of iodothyronines on liver lipid metabolism results from the balance between direct and indirect actions on the hepatocyte, leading to stimulation of lipid synthesis, oxidation and autophagy. In this review, the results so far obtained on both in vivo and in vitro models of hepatosteatosis are summarized in order to obtain an updated picture of the lipid-lowering effects of iodothyronines on mammalian liver.

Keywords: Hepatocytes; Iodothyronines; Lipid metabolism; Liver steatosis; Non-alcoholic fatty liver disease.

PubMed Disclaimer

Figures

Figure 1

Figure 1

The chemical structures of three biologically active iodothyronines and one derivative: thyroxine, 3,3’,5-triiodothyronine, 3,5-diiodothyronine and 3-iodothyronamine. T4: Thyroxine; T3: 3,3’,5-triiodothyronine; T2: 3,5-diiodothyronine; T1AM: 3-iodothyronamine.

Figure 2

Figure 2

Schematic representation of the mechanisms underlying the control of lipid metabolism by iodothyronines in the hepatic cell: A summary of the possible signaling pathways involved in iodothyronine actions is presented. The classic “receptor-mediated” pathway describes the action of iodothyronines through the thyroid hormone receptors (TR). The “non receptor-mediated” pathway occurs through the interaction of iodothyronines with different cellular targets. FFA: Free fatty acids; LD: Lipid droplet; AOX: Acyl-CoA oxidase; ATGL: Adipose triglyceride lipase; CPT: Carnitine palmitoyl-transferase 1; FAS: fatty acid synthase.

References

    1. Goglia F. Biological effects of 3,5-diiodothyronine (T(2)) Biochemistry (Mosc) 2005;70:164–172. - PubMed
    1. Hulbert AJ. Thyroid hormones and their effects: a new perspective. Biol Rev Camb Philos Soc. 2000;75:519–631. - PubMed
    1. Ness GC, Lopez D. Transcriptional regulation of rat hepatic low-density lipoprotein receptor and cholesterol 7 alpha hydroxylase by thyroid hormone. Arch Biochem Biophys. 1995;323:404–408. - PubMed
    1. Lopez D, Abisambra Socarrás JF, Bedi M, Ness GC. Activation of the hepatic LDL receptor promoter by thyroid hormone. Biochim Biophys Acta. 2007;1771:1216–1225. - PubMed
    1. Cunningham BA, Moncur JT, Huntington JT, Kinlaw WB. “Spot 14” protein: a metabolic integrator in normal and neoplastic cells. Thyroid. 1998;8:815–825. - PubMed

Publication types

LinkOut - more resources