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

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
PLoS One ; 9(1): e85636, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24454908

RESUMO

We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3). Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER), indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPARδ expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction.


Assuntos
Músculo Esquelético/enzimologia , Sirtuína 3/fisiologia , Animais , Citrato (si)-Sintase/metabolismo , Creatina Quinase Forma MM/metabolismo , Feminino , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Transgênicos , Mitocôndrias Musculares/metabolismo , Força Muscular , Músculo Esquelético/citologia , Músculo Esquelético/crescimento & desenvolvimento , Oxirredução , Consumo de Oxigênio , Esforço Físico , Regulação para Cima
2.
Aging (Albany NY) ; 1(9): 771-83, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-20157566

RESUMO

SIRT3 is a member of the sirtuin family of NAD(+)-dependent deacetylases, which is localized to the mitochondria and is enriched in kidney, brown adipose tissue, heart, and other metabolically active tissues. We report here that SIRT3 responds dynamically to both exercise and nutritional signals in skeletal muscle to coordinate downstream molecular responses. We show that exercise training increases SIRT3 expression as well as associated CREB phosphorylation and PGC-1alpha up-regulation. Furthermore, we show that SIRT3 is more highly expressed in slow oxidative type I soleus muscle compared to fast type II extensor digitorum longus or gastrocnemius muscles. Additionally, we find that SIRT3 protein levels in skeletal muscle are sensitive to diet, for SIRT3 expression increases by fasting and caloric restriction, yet it is decreased by high-fat diet. Interestingly, the caloric restriction regimen also leads to phospho-activation of AMPK in muscle. Conversely in SIRT3 knockout mice, we find that the phosphorylation of both AMPK and CREB and the expression of PGC-1alpha are down regulated, suggesting that these key cellular factors may be important components of SIRT3-mediated biological signals in vivo.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Dieta , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Sirtuína 3/metabolismo , Transativadores/metabolismo , Estruturas Animais/metabolismo , Animais , Restrição Calórica , Citrato (si)-Sintase/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Jejum/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fosforilação/genética , Caracteres Sexuais , Sirtuína 3/genética , Fatores de Transcrição
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA