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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Regulation of Lin28a-miRNA let-7b-5p pathway in skeletal muscle cells by peroxisome proliferator-activated receptor delta

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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]
Total Authors: 16
Affiliation:
[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
Total Affiliations: 6
Document type: Journal article
Source: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY; v. 319, n. 3, p. C541-C551, SEP 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 13/22733-0 - Effect of miR-696 e miR-let7b on the mitochondrial function in insulin resistant muscle cells
Grantee:Leonardo dos Reis Silveira
Support Opportunities: Regular Research Grants
FAPESP's process: 16/23008-5 - Identification and functional characterization of protein bound to NCoR1 complex and associated with molecular control of mitochondrial biogenesis process
Grantee:Leonardo dos Reis Silveira
Support Opportunities: Research Projects - Thematic Grants