title: Thyroid hormone regulation of Sirtuin 1 expression and implications to integrated responses in fasted mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Aline
authors.initials: A
authors.lastname: Cordeiro
authors.forename: Luana Lopes
authors.initials: LL
authors.lastname: de Souza
authors.forename: Lorraine Soares
authors.initials: LS
authors.lastname: Oliveira
authors.forename: Larissa Costa
authors.initials: LC
authors.lastname: Faustino
authors.forename: Letícia Aragão
authors.initials: LA
authors.lastname: Santiago
authors.forename: Flavia Fonseca
authors.initials: FF
authors.lastname: Bloise
authors.forename: Tania Maria
authors.initials: TM
authors.lastname: Ortiga-Carvalho
authors.forename: Norma Aparecida Dos Santos
authors.initials: NA
authors.lastname: Almeida
authors.forename: Carmen Cabanelas
authors.initials: CC
authors.lastname: Pazos-Moura
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D031204:Caloric Restriction; D004435:Eating / Q000235:genetics / Q000502:physiology; D006980:Hyperthyroidism / Q000235:genetics / Q000378:metabolism; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood* / Q000378:metabolism
chemical_list: D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D056564:Sirtuin 1