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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Skeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition

Texto completo
Autor(es):
Cruz, Andre [1] ; Ferian, Andrea [1] ; Alves, Paula K. N. [1] ; Silva, William Jose [1] ; Bento, Mirella Ribeiro [1] ; Gasch, Alexander [2] ; Labeit, Siegfried [2] ; Moriscot, Anselmo Sigari [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil
[2] Heidelberg Univ, Inst Integrat Pathophysiol, Fac Clin Med Mannheim, Mannheim - Germany
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: DNA AND CELL BIOLOGY; v. 39, n. 12 NOV 2020.
Citações Web of Science: 0
Resumo

Lack of mechanical load leads to skeletal muscle atrophy, and one major underlying mechanism involves the myostatin pathway that negatively regulates protein synthesis and also activates Atrogin-1/MAFbx and MuRF1 genes. In hindlimb immobilization, leucine was observed to attenuate the upregulation of the referred atrogenes, thereby shortening the impact on fiber cross-sectional area, nonetheless, the possible connection with myostatin is still elusive. This study sought to verify the impact of leucine supplementation on myostatin expression. Male Wistar rats were supplemented with leucine and hindlimb immobilized for 3 and 7 days, after which soleus muscles were removed for morphometric measurements and analyzed for gene and protein expression by real-time PCR and Western blotting, respectively. Muscle wasting was prominent 7 days after immobilization, as expected, leucine feeding mitigated this effect. Atrogin-1/MAFbx gene expression was upregulated only after 3 days of immobilization, and this effect was attenuated by leucine supplementation. Atrogin-1/MAFbx protein levels were elevated after 7 days of immobilization, which leucine supplementation was not able to lessen. On the other hand, myostatin gene expression was upregulated in immobilization for 3 and 7 days, which returned to normal levels after leucine supplementation. Myostatin protein levels followed gene expression at a 3-day time point only. Follistatin gene expression was upregulated during immobilization and accentuated by leucine after 3 days of supplementation. Concerning protein expression, follistatin was not altered neither by immobilization nor in immobilized animals treated with leucine. In conclusion, leucine protects against skeletal muscle mass loss during disuse, and the underlying molecular mechanisms appear to involve myostatin inhibition and Atrogin-1 normalization independently of follistatin signaling. (AU)

Processo FAPESP: 12/22488-2 - Expressão de microRNAs em plasticidade muscular esquelética: possíveis inter-relações com o efeito de MuRFs no processo regenerativo
Beneficiário:William Jose da Silva
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 13/19387-2 - Regulação da via GSK3-beta/Beta-catenina no músculo esquelético de ratos suplementados com leucina e submetidos à atrofia
Beneficiário:Mirella Ribeiro Bento
Linha de fomento: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 15/04090-0 - Identificação e caracterização de mecanismos envolvidos no controle de massa e regeneração do músculo estriado esquelético
Beneficiário:Anselmo Sigari Moriscot
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/09398-8 - Interações entre as vias da miostatina e mTORC1 no músculo esquelético: implicações para a ação biológica do hormônio tireoidiano
Beneficiário:André Cruz de Oliveira
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 18/24419-4 - Efeito da leucina sobre a expressão de miR-299A e HDAC4 no músculo esquelético de ratos submetidos à imobilização: implicações para o controle de massa muscular
Beneficiário:Paula Ketilly Nascimento Alves
Linha de fomento: Bolsas no Brasil - Doutorado Direto