Document Detail

Thyroid hormone regulation of Sirtuin 1 expression and implications to integrated responses in fasted mice.
MedLine Citation:
PMID:  23151359     Owner:  NLM     Status:  MEDLINE    
Sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, has been connected to beneficial effects elicited by calorie restriction. Physiological adaptation to starvation requires higher activity of SIRT1 and also the suppression of thyroid hormone (TH) action to achieve energy conservation. Here, we tested the hypothesis that those two events are correlated and that TH may be a regulator of SIRT1 expression. Forty-eight-hour fasting mice exhibited reduced serum TH and increased SIRT1 protein content in liver and brown adipose tissue (BAT), and physiological thyroxine replacement prevented or attenuated the increment of SIRT1 in liver and BAT of fasted mice. Hypothyroid mice exhibited increased liver SIRT1 protein, while hyperthyroid ones showed decreased SIRT1 in liver and BAT. In the liver, decreased protein is accompanied by reduced SIRT1 activity and no alteration in its mRNA. Hyperthyroid and hypothyroid mice exhibited increases and decreases in food intake and body weight gain respectively. Food-restricted hyperthyroid animals (pair-fed to euthyroid group) exhibited liver and BAT SIRT1 protein levels intermediary between euthyroid and hyperthyroid mice fed ad libitum. Mice with TH resistance at the liver presented increased hepatic SIRT1 protein and activity, with no alteration in Sirt1 mRNA. These results suggest that TH decreases SIRT1 protein, directly and indirectly, via food ingestion control and, in the liver, this reduction involves TRβ. The SIRT1 reduction induced by TH has important implication to integrated metabolic responses to fasting, as the increase in SIRT1 protein requires the fasting-associated suppression of TH serum levels.
Aline Cordeiro; Luana Lopes de Souza; Lorraine Soares Oliveira; Larissa Costa Faustino; Letícia Aragão Santiago; Flavia Fonseca Bloise; Tania Maria Ortiga-Carvalho; Norma Aparecida Dos Santos Almeida; Carmen Cabanelas Pazos-Moura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-18
Journal Detail:
Title:  The Journal of endocrinology     Volume:  216     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-03-11     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  181-93     Citation Subset:  IM    
Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Cidade Universitária - Ilha do Fundão, Avenida Carlos Chagas Filho, 373, Centro de Ciências da Saúde, Bloco G, CEP: 21941-902, Rio de Janeiro, RJ, Brazil.
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MeSH Terms
Body Weight / genetics,  physiology
Caloric Restriction
Eating / genetics,  physiology
Hyperthyroidism / genetics,  metabolism
Hypothyroidism / genetics,  metabolism
Mice, Transgenic
Sirtuin 1 / genetics,  metabolism*
Thyroid Hormone Receptors beta / metabolism
Thyroid Hormones / blood*,  metabolism
Reg. No./Substance:
0/Thyroid Hormone Receptors beta; 0/Thyroid Hormones; EC 3.5.1.-/Sirtuin 1

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