| Texto completo | |
| Autor(es): Mostrar menos - |
Araujo, Hygor N.
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Lima, Tanes I.
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Guimaraes, Dimitrius Santiago P. S. F.
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Oliveira, Andre G.
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Favero-Santos, Bianca C.
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Branco, Renato C. S.
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da Silva Araujo, Rafaela Mariano
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Dantas, Alvaro F. B.
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Castro, Alex
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Chacon-Mikahil, Mara Patricia T.
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Minatel, Elaine
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Geraldo, Murilo V.
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Carneiro, Everardo Magalhaes
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Rodrigues, Alice C.
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Narkar, Vihang A.
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Silveira, Leonardo R.
Número total de Autores: 16
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| Tipo de documento: | Artigo Científico |
| Fonte: | AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY; v. 319, n. 3, p. 11-pg., 2020-09-22. |
| Resumo | |
Regulation of Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that 8 wk of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) increased its expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression. Bioinformatics analysis of LIN28a DNA sequence revealed that its enrichment in peroxisome proliferator-activated receptor delta (PPAR delta) binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPAR delta activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression was also regulated by PPAR delta coregulators. While PPAR gamma coactivator-1 alpha (PGC1 alpha) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1 alpha markedly reduced the let-7b-5p expression. PGC1 alpha-mediated induction of Lin28a expression was blocked by the PPAR delta inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPAR delta knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a-let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1 alpha dependent fashion. In summary, we demonstrate that Lin28a-let-7b-5p is a direct target of PPAR delta in the skeletal muscle, where it impacts mitochondrial respiration. (AU) | |
| Processo FAPESP: | 13/22733-0 - Controle da função mitocondrial por micro-RNAs em células musculares resistentes a insulina: efeito da superexpressão e inibição do miR-696 e miR-let7b |
| Beneficiário: | Leonardo dos Reis Silveira |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 16/23008-5 - Identificação e caracterização funcional de proteína do complexo NCoR1 associada ao controle molecular do processo de biogênese mitocondrial |
| Beneficiário: | Leonardo dos Reis Silveira |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |