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

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.

The transcription of iodothyronine deiodinase genes is regulated by thyroid hormone receptor in the Pacific oyster Crassostrea gigas

Thyroid hormones (THs) are indispensable for each phyla in Chordata, while their functions in the non-chordate invertebrates are indistinct. Studies on the TH system in non-chordate invertebrates are important for understanding the evolution of TH system and may be applied in aquaculture or biofouling control at the same time. Iodothyronine deiodinases are keys to studying the TH system, as they are critical enzymes in maintaining TH homeostasis by catalyzing the initiation and termination of the effects of thyroid hormone in vertebrates. Here, we report the primary physiological effects of T4, the outer ring deiodinase activity, and a similar transcription regulation of two oyster deiodinases by TH receptor (CgTR) in an invertebrate, Pacific oyster Crassostrea gigas. L-thyroxine (T4) may have an important physiological function in the oyster, suggested by the growth retardation effect of excessive T4 in umbo larvae stage. The outer ring deiodinase activity transforming T4 to T3 (3, 3', 5-triiodothyronine) was then detected in the Pacific oyster in vivo, which may be conducted by two oyster deiodinases (CgDx and CgDy). Transcription regulation of CgTR onto these two deiodinase genes was also verified by electrophoretic mobility shift assay and dual luciferase reporter assay in mammalian cells. These results contribute to a better understanding of the evolution of the TH system.

Biological Functions of Selenoprotein Iodothyronine Deiodinase and its Expression in Osteoarthritis

Objective Iodothyronine deiodinases(DIOs)are important selenoproteins that play a key role in the bone and joint diseases.Osteoarthritis(OA)is the most prevalent joint disease especially in elders.This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis.Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques,mcluding GenCLip 3.0,Database for Annotation,Visualization and Integrated Discovery(DAVID),STRING,Cytoscape,and Network Analyst.The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus(GEO)database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3.Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine;GO analysis showed that DIOs were mainly involved in biological processes,such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling;SULT1A1 was the core node of the PPI network;miRNAs and thyroid hormones had some iterations with DIO1 and DI02;Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients(SMD=0.31,95%CI:0.03,0.59,P=0.03).Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone.And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.