Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
PLoS One ; 14(8): e0220717, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404087

RESUMO

Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) and the nuclear receptor co-repressor1 (NCoR1) are paralogs and regulate nuclear receptor (NR) function through the recruitment of a multiprotein complex that includes histone deacetylase activity. Previous genetic strategies which deleted SMRT in a specific tissue or which altered the interaction between SMRT and NRs have suggested that it may regulate adiposity and insulin sensitivity. However, the full role of SMRT in adult mice has been difficult to establish because its complete deletion during embryogenesis is lethal. To elucidate the specific roles of SMRT in mouse target tissues especially in the context of thyroid hormone (TH) signaling, we used a tamoxifen-inducible post-natal disruption strategy. We found that global SMRT deletion causes dramatic obesity even though mice were fed a standard chow diet and exhibited normal food intake. This weight gain was associated with a decrease in energy expenditure. Interestingly, the deletion of SMRT had no effect on TH action in any tissue but did regulate retinoic acid receptor (RAR) function in the liver. We also demonstrate that the deletion of SMRT leads to profound hepatic steatosis in the setting of obesity. This is unlike NCoR1 deletion, which results in hepatic steatosis due to the upregulation of lipogenic gene expression. Taken together, our data demonstrate that SMRT plays a unique and CoR specific role in the regulation of body weight and has no role in TH action. This raises the possibility that additional role of CoRs besides NCoR1 and SMRT may exist to regulate TH action.


Assuntos
Peso Corporal/fisiologia , Correpressor 2 de Receptor Nuclear/fisiologia , Hormônios Tireóideos/fisiologia , Animais , Western Blotting , Colesterol/análise , Ecocardiografia , Metabolismo Energético , Teste de Tolerância a Glucose , Lipídeos/sangue , Fígado/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Hormônios Tireóideos/sangue , Tireotropina/sangue , Tireotropina/fisiologia , Tiroxina/sangue , Tiroxina/fisiologia , Triglicerídeos/análise , Aumento de Peso/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...