Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Endocrinology ; 161(10)2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32770234

RESUMO

The Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) is a nuclear corepressor, regulating the transcriptional activity of many transcription factors critical for metabolic processes. While the importance of the role of SMRT in the adipocyte has been well-established, our comprehensive understanding of its in vivo function in the context of homeostatic maintenance is limited due to contradictory phenotypes yielded by prior generalized knockout mouse models. Multiple such models agree that SMRT deficiency leads to increased adiposity, although the effects of SMRT loss on glucose tolerance and insulin sensitivity have been variable. We therefore generated an adipocyte-specific SMRT knockout (adSMRT-/-) mouse to more clearly define the metabolic contributions of SMRT. In doing so, we found that SMRT deletion in the adipocyte does not cause obesity-even when mice are challenged with a high-fat diet. This suggests that adiposity phenotypes of previously described models were due to effects of SMRT loss beyond the adipocyte. However, an adipocyte-specific SMRT deficiency still led to dramatic effects on systemic glucose tolerance and adipocyte insulin sensitivity, impairing both. This metabolically deleterious outcome was coupled with a surprising immune phenotype, wherein most genes differentially expressed in the adipose tissue of adSMRT-/- mice were upregulated in pro-inflammatory pathways. Flow cytometry and conditioned media experiments demonstrated that secreted factors from knockout adipose tissue strongly informed resident macrophages to develop a pro-inflammatory, MMe (metabolically activated) phenotype. Together, these studies suggest a novel role for SMRT as an integrator of metabolic and inflammatory signals to maintain physiological homeostasis.


Assuntos
Tecido Adiposo/metabolismo , Diferenciação Celular/genética , Metabolismo Energético/genética , Macrófagos/fisiologia , Correpressor 2 de Receptor Nuclear/fisiologia , Adipócitos/fisiologia , Tecido Adiposo/citologia , Animais , Homeostase/genética , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Correpressor 2 de Receptor Nuclear/genética , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Especificidade de Órgãos/genética , Fenótipo
2.
Mol Cell Endocrinol ; 407: 52-6, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25766503

RESUMO

Local modulation of glucocorticoid action in adipocytes regulates adiposity and systemic insulin sensitivity. However, the specific cofactors that mediate glucocorticoid receptor (GR) action in adipocytes remain unclear. Here we show that the silencing mediator of retinoid and thyroid hormone receptors (SMRT) is recruited to GR in adipocytes and regulates ligand-dependent GR function. Decreased SMRT expression in adipocytes in vivo increases expression of glucocorticoid-responsive genes. Moreover, adipocytes with decreased SMRT expression exhibit altered glucocorticoid regulation of lipolysis. We conclude that SMRT regulates the metabolic functions of GR in adipocytes in vivo. Modulation of GR-SMRT interactions in adipocytes represents a novel approach to control the local degree of glucocorticoid action and thus influence adipocyte metabolic function.


Assuntos
Adipócitos/efeitos dos fármacos , Dexametasona/farmacologia , Correpressor 2 de Receptor Nuclear/genética , Receptores de Glucocorticoides/genética , Receptores dos Hormônios Tireóideos/genética , Adipócitos/citologia , Adipócitos/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Epididimo/citologia , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Lipólise/efeitos dos fármacos , Lipólise/genética , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Correpressor 2 de Receptor Nuclear/metabolismo , Fosfatidato Fosfatase/genética , Fosfatidato Fosfatase/metabolismo , Cultura Primária de Células , Transporte Proteico , Receptor Cross-Talk , Receptores de Glucocorticoides/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...