Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros

Bases de dados
Tipo de documento
Assunto da revista
País de afiliação
Intervalo de ano de publicação
1.
BMC Genomics ; 16: 820, 2015 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-26482036

RESUMO

BACKGROUND: In small mammals brown adipose tissue (BAT) plays a predominant role in regulating energy expenditure (EE) via adaptive thermogenesis. New-born babies require BAT to control their body temperature, however its relevance in adults has been questioned. Active BAT has recently been observed in adult humans, albeit in much lower relative quantities than small mammals. Comparing and contrasting the molecular mechanisms controlling BAT growth and development in mice and humans will increase our understanding or how human BAT is developed and may identify potential therapeutic targets to increase EE. MicroRNAs are molecular mechanisms involved in mouse BAT development however, little is known about the miRNA profile in human BAT. The aims of this study were to establish a mouse BAT-enriched miRNA profile and compare this with miRNAs measured in human BAT. To achieve this we firstly established a mouse BAT enriched-miRNA profile by comparing miRNAs expressed in mouse BAT, white adipose tissue and skeletal muscle. Following this the BAT-enriched miRNAs predicted to target genes potentially involved in growth and development were identified. METHODS: MiRNA levels were measured using PCR-based miRNA arrays. Results were analysed using ExpressionSuite software with the global mean expression value of all expressed miRNAs in a givensample used as the normalisation factor. Bio-informatic analyses was used to predict gene targets followed by Ingenuity Pathway Analysis. RESULTS: We identified 35 mouse BAT-enriched miRNAs that were predicted to target genes potentially involved in growth and development. We also identified 145 miRNAs expressed in both mouse and human BAT, of which 25 were enriched in mouse BAT. Of these 25 miRNAs, miR-20a was predicted to target MYF5 and PPARγ, two important genes involved in brown adipogenesis, as well as BMP2 and BMPR2, genes involved in white adipogenesis. For the first time, 69 miRNAs were identified in human BAT but absent in mouse BAT, and 181 miRNAs were expressed in mouse but not in human BAT. CONCLUSION: The present study has identified a small sub-set of miRNAs common to both mouse and human BAT. From this sub-set bioinformatics analysis suggested a potential role of miR-20a in the control of cell fate and this warrants further investigation. The large number of miRNAs found only in mouse BAT or only in human BAT highlights the differing molecular profile between species that is likely to influence the functional role of BAT across species. Nevertheless the BAT-enriched miRNA profiles established in the present study suggest targets to investigate in the control BAT development and EE.


Assuntos
Adipogenia/genética , Tecido Adiposo Marrom , Metabolismo Energético/genética , MicroRNAs/biossíntese , Termogênese/genética , Adulto , Animais , Diferenciação Celular/genética , Biologia Computacional , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos
2.
J Physiol ; 591(18): 4637-53, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23798494

RESUMO

The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P=0.04), miR-31 and HDAC4 protein (r=-0.87; P=0.026) and miR-31 and NRF1 protein (r=-0.77; P=0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3 untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health.


Assuntos
Exercício Físico , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Resistência Física , Adulto , Biologia Computacional , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Masculino , MicroRNAs/genética , Músculo Esquelético/fisiologia , Fator 1 Nuclear Respiratório/genética , Fator 1 Nuclear Respiratório/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Ribonuclease III/genética , Ribonuclease III/metabolismo
3.
J Physiol ; 588(Pt 21): 4075-87, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-20724363

RESUMO

Maintaining skeletal muscle function throughout the lifespan is a prerequisite for good health and independent living. For skeletal muscle to consistently function at optimal levels, the efficient activation of processes that regulate muscle development, growth, regeneration and metabolism is required. Numerous conditions including neuromuscular disorders, physical inactivity, chronic disease and ageing are associated with perturbations in skeletal muscle function. A loss or reduction in skeletal muscle function often leads to increased morbidity and mortality either directly, or indirectly, via the development of secondary diseases such as diabetes, obesity, cardiovascular and respiratory disease. Identifying mechanisms which influence the processes regulating skeletal muscle function is a key priority. The discovery of microRNAs (miRNAs) provides a new avenue that will extend our knowledge of factors controlling skeletal muscle function. miRNAs may also improve our understanding and application of current therapeutic approaches as well as enable the identification of new therapeutic strategies and targets aimed at maintaining and/or improving skeletal muscle health. This review brings together the latest developments in skeletal muscle miRNA biology and focuses on their role and regulation under physiological and patho-physiological conditions with an emphasis on: myogenesis, hypertrophy, atrophy and regeneration; exercise and nutrition; muscle disease, ageing, diabetes and obesity.


Assuntos
MicroRNAs/fisiologia , Músculo Esquelético/fisiologia , Músculo Esquelético/fisiopatologia , Envelhecimento/fisiologia , Animais , Diabetes Mellitus/fisiopatologia , Exercício Físico/fisiologia , Humanos , Desenvolvimento Muscular/fisiologia , Doenças Musculoesqueléticas/fisiopatologia
4.
Diabetes ; 58(11): 2555-64, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19720801

RESUMO

OBJECTIVE: Factors governing microRNA expressions in response to changes of cellular environment are still largely unknown. Our aim was to determine whether insulin, the major hormone controlling whole-body energy homeostasis, is involved in the regulation of microRNA expressions in human skeletal muscle. RESEARCH DESIGN AND METHODS: We carried out comparative microRNA (miRNA) expression profiles in human skeletal muscle biopsies before and after a 3-h euglycemic-hyperinsulinemic clamp, with TaqMan low-density arrays. Then, using DNA microarrays, we determined the response to insulin of the miRNA putative target genes in order to determine their role in the transcriptional action of insulin. We further characterized the mechanism of action of insulin on two representative miRNAs, miR-1 and miR-133a, in human muscle cells. RESULTS: Insulin downregulated the expressions of 39 distinct miRNAs in human skeletal muscle. Their potential target mRNAs coded for proteins that were mainly involved in insulin signaling and ubiquitination-mediated proteolysis. Bioinformatic analysis suggested that combinations of different downregulated miRNAs worked in concert to regulate gene expressions in response to insulin. We further demonstrated that sterol regulatory element-binding protein (SREBP)-1c and myocyte enhancer factor 2C were involved in the effect of insulin on miR-1 and miR-133a expression. Interestingly, we found an impaired regulation of miRNAs by insulin in the skeletal muscle of type 2 diabetic patients, likely as consequences of altered SREBP-1c activation. CONCLUSIONS: This work demonstrates a new role of insulin in the regulation of miRNAs in human skeletal muscle and suggests a possible implication of these new modulators in insulin resistance.


Assuntos
Insulina/genética , MicroRNAs/genética , Músculo Esquelético/fisiologia , Fatores de Regulação Miogênica/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/fisiologia , Transcrição Gênica , Biópsia , Linhagem Celular , DNA Complementar/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Regulação para Baixo , Regulação da Expressão Gênica , Técnica Clamp de Glucose , Humanos , Hiperglicemia/fisiopatologia , Hiperinsulinismo/fisiopatologia , Fatores de Transcrição MEF2 , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Valores de Referência , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA