| Texto completo | |
| Autor(es): Mostrar menos - |
Araujo, Hygor N.
[1]
;
Lima, I, Tanes
;
Guimaraes, Dimitrius Santiago P. S. F.
[2]
;
Oliveira, Andre G.
[2]
;
Favero-Santos, Bianca C.
[2]
;
Branco, Renato C. S.
[2]
;
da Silva Araujo, Rafaela Mariano
[2]
;
Dantas, Alvaro F. B.
[2]
;
Castro, Alex
[3]
;
Chacon-Mikahil, Mara Patricia T.
[3]
;
Minatel, Elaine
[4]
;
Geraldo, V, Murilo
;
Carneiro, Everardo Magalhaes
[2]
;
Rodrigues, Alice C.
[5]
;
Narkar, Vihang A.
[6]
;
Silveira, Leonardo R.
[2]
Número total de Autores: 16
|
| Afiliação do(s) autor(es): | [1] Obes & Comorbid Res Ctr OCRC, Campinas - Brazil
[2] Lima, Tanes, I, Obes & Comorbid Res Ctr OCRC, Campinas - Brazil
[3] Univ Estadual Campinas, Sch Phys Educ, Lab Exercise Physiol, Campinas - Brazil
[4] V, Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, UNICAMP, Campinas - Brazil
[5] Univ Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil
[6] Univ Texas Hlth McGovern Med Sch, Inst Mol Med, Houston, TX 77030 - USA
Número total de Afiliações: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY; v. 319, n. 3, p. C541-C551, SEP 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
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-76-5p 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-clown cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a-let-76-5p 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 |