JOURNAL ARTICLE

Regulation of Lin28a-miRNA let-7b-5p pathway in the skeletal muscle cells by PPARδ

Hygor N Araujo, Tanes I Lima, Dimitrius Santiago P S F Guimarães, Andre G Oliveira, Bianca C Favero-Santos, Renato C S Branco, Rafaela Mariano da Silva Araújo, Alvaro F B Dantas, Alex Castro, Mara Patrícia T Chacon-Mikahill, Elaine Minatel, Murilo V Geraldo, Everardo Magalhães Carneiro, Alice C Rodrigues, Vihang A Narkar, Leonardo R Silveira
American Journal of Physiology. Cell Physiology 2020 July 22
32697599
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 eight weeks of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) decreased it's 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 it is enrichment in PPARδ binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPARδ activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression were also regulated by PPARδ co-regulators. While co-activator PGC1α increased Lin28a expression, co-repressor NCoR1 decreased it's expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by PPARδ inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPARδ knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of Lin28a-let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1α dependent fashion. In summary, we demonstrate that Lin28a-let-7b-5p is a direct target of PPARδ in the skeletal muscle, where its impacts mitochondrial respiration.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
32697599
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"