Please use this identifier to cite or link to this item:
Title: Changes in hepatic TRβ protein expression, lipogenic gene expression, and long-chain acylcarnitine levels during chronic hyperthyroidism and triiodothyronine withdrawal in a mouse model
Authors: Ohba K. 
Sinha R.A. 
Singh B.K. 
Iannucci L.F.
Zhou J. 
Kovalik J.-P. 
Liao X.-H.
Refetoff S.
Sng J.C.G. 
Leow M.K.-S. 
Yen P.M. 
Keywords: gene expression
temporal adaptation
thyroid hormone receptor
ubiquitin-proteasome pathway
Issue Date: 2017
Publisher: Mary Ann Liebert Inc.
Citation: Ohba K., Sinha R.A., Singh B.K., Iannucci L.F., Zhou J., Kovalik J.-P., Liao X.-H., Refetoff S., Sng J.C.G., Leow M.K.-S., Yen P.M. (2017). Changes in hepatic TRβ protein expression, lipogenic gene expression, and long-chain acylcarnitine levels during chronic hyperthyroidism and triiodothyronine withdrawal in a mouse model. Thyroid 27 (6) : 852 - 860. ScholarBank@NUS Repository.
Abstract: Background: Thyroid hormone (TH) has important roles in regulating hepatic metabolism. It was previously reported that most hepatic genes activated by a single triiodothyronine (T3) injection became desensitized after multiple injections, and that approximately 10% of target genes did not return to basal expression levels after T3 withdrawal, despite normalization of serum TH and thyrotropin (TSH) levels. To determine the possible mechanism(s) for desensitization and incomplete recovery of hepatic target gene transcription and their effects on metabolism, mRNA and/or protein expression levels of key regulators of TH action were measured, as well as metabolomic changes after chronic T3 treatment and withdrawal. Methods: Adult male mice were treated with daily injections of T3 (20 ?g/100 g body weight) for 14 days followed by the cessation of T3 for 10 days. Livers were harvested at 6 hours, 24 hours, and 14 days after the first T3 injection, and at 10 days after withdrawal, and then analyzed by quantitative reverse transcription polymerase chain reaction, Western blotting, and metabolomics. Results: Although TH receptor (TR? and TR?) mRNAs decreased slightly after chronic T3 treatment, only TR? protein decreased before returning to basal expression level after withdrawal. The expression of other regulators of TH action was unchanged. TR? protein expression was also decreased in adult male monocarboxylate transporter-8 (Mct8)-knockout mice, an in vivo model of chronic intrahepatic hyperthyroidism. Previously, increased hepatic long-chain acylcarnitine levels were found after acute TH treatment. However, in this study, long-chain acylcarnitine levels were unchanged after chronic T3, and paradoxically increased after T3 withdrawal. Pathway analyses of the previous microarray results showed upregulation of lipogenic genes after acute T3 treatment and withdrawal. Phosphorylation of acetyl-CoA carboxylase also decreased after T3 withdrawal. Conclusions: Decreased hepatic TR? protein expression occurred after chronic T3 exposure in adult male wild-type and Mct8-knockout mice. Gene array pathway and metabolomics analyses showed abnormalities in hepatic lipogenic gene expression and acylcarnitine levels, respectively, after withdrawal, despite normalization of serum TSH and TH levels. These findings may help explain the variable clinical presentations of some patients during hyperthyroidism and recovery, since TR? protein, target gene expression, and metabolic adaptive changes can occur in individual tissues without necessarily being reflected by circulating TH and TSH concentrations. Copyright 2017, Mary Ann Liebert, Inc. 2017.
Source Title: Thyroid
ISSN: 10507256
DOI: 10.1089/thy.2016.0456
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.