scholarly journals The peroxisome proliferator-activated receptor γ coactivator 1α/β (PGC-1) coactivators repress the transcriptional activity of NF-κB in skeletal muscle cells.

2013 ◽  
Vol 288 (9) ◽  
pp. 6589-6589 ◽  
Author(s):  
Petra S. Eisele ◽  
Silvia Salatino ◽  
Jens Sobek ◽  
Michael O. Hottiger ◽  
Christoph Handschin
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activity ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

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

2020 ◽  
Vol 319 (3) ◽  
pp. C541-C551
Author(s):  
Hygor N. Araujo ◽  
Tanes I. Lima ◽  
Dimitrius Santiago P. S. F. Guimarães ◽  
Andre G. Oliveira ◽  
Bianca C. Favero-Santos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Homeostasis ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
Skeletal Muscle Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Primary Mouse ◽  
Murine Skeletal Muscle ◽  
Muscle Biopsies

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 (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 was also regulated by PPARδ coregulators. While PPARγ coactivator-1α (PGC1α) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by the 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 the 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 it impacts mitochondrial respiration.

scholarly journals Activation of Peroxisome Proliferator-Activated Receptor-δ by GW501516 Prevents Fatty Acid-Induced Nuclear Factor-κB Activation and Insulin Resistance in Skeletal Muscle Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1560-1569 ◽  
Author(s):  
Teresa Coll ◽  
David Álvarez-Guardia ◽  
Emma Barroso ◽  
Anna Maria Gómez-Foix ◽  
Xavier Palomer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Carnitine Palmitoyltransferase 1

Elevated plasma free fatty acids cause insulin resistance in skeletal muscle through the activation of a chronic inflammatory process. This process involves nuclear factor (NF)-κB activation as a result of diacylglycerol (DAG) accumulation and subsequent protein kinase Cθ (PKCθ) phosphorylation. At present, it is unknown whether peroxisome proliferator-activated receptor-δ (PPARδ) activation prevents fatty acid-induced inflammation and insulin resistance in skeletal muscle cells. In C2C12 skeletal muscle cells, the PPARδ agonist GW501516 prevented phosphorylation of insulin receptor substrate-1 at Ser307 and the inhibition of insulin-stimulated Akt phosphorylation caused by exposure to the saturated fatty acid palmitate. This latter effect was reversed by the PPARδ antagonist GSK0660. Treatment with the PPARδ agonist enhanced the expression of two well known PPARδ target genes involved in fatty acid oxidation, carnitine palmitoyltransferase-1 and pyruvate dehydrogenase kinase 4 and increased the phosphorylation of AMP-activated protein kinase, preventing the reduction in fatty acid oxidation caused by palmitate exposure. In agreement with these changes, GW501516 treatment reversed the increase in DAG and PKCθ activation caused by palmitate. These effects were abolished in the presence of the carnitine palmitoyltransferase-1 inhibitor etomoxir, thereby indicating that increased fatty acid oxidation was involved in the changes observed. Consistent with these findings, PPARδ activation by GW501516 blocked palmitate-induced NF-κB DNA-binding activity. Likewise, drug treatment inhibited the increase in IL-6 expression caused by palmitate in C2C12 and human skeletal muscle cells as well as the protein secretion of this cytokine. These findings indicate that PPARδ attenuates fatty acid-induced NF-κB activation and the subsequent development of insulin resistance in skeletal muscle cells by reducing DAG accumulation. Our results point to PPARδ activation as a pharmacological target to prevent insulin resistance.

α-amyrin induce GLUT4 translocation mediated by AMPK and PPARδ/γ in C2C12 myoblasts

2021 ◽  
Author(s):  
Abraham Giacoman-Martínez ◽  
Francisco Javier Alarcón-Aguilar ◽  
Alejandro Zamilpa-Alvarez ◽  
Fengyang Huang ◽  
Rodrigo Romero ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Transporter ◽  
Metabolic Diseases ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Peroxisome Proliferator ◽  
Glut4 Translocation ◽  
Pentacyclic Triterpene ◽  
C2c12 Myoblasts

α-amyrin, a natural pentacyclic triterpene, have anti-hyperglycemic effect in mice and dual PPARδ/γ action in 3T3-L1 adipocytes, and potential in the control of type 2 diabetes (T2D). About 80% of glucose uptake occurs in skeletal muscle cells, playing a significant role in IR and T2D. Peroxisome-proliferator activated receptors (PPARs), in particular PPARδ and PPARγ, are involved in the regulation of lipids and carbohydrates and, along adenosine-monophosphate (AMP)-activated protein kinase (AMPK) and protein kinase B (Akt/PKB), are implicated in translocation of glucose transporter 4 (GLUT4). However, it is still unknown whether α-amyrin can affect these pathways in skeletal muscle cells. The work's objective was to determine the action of α-amyrin in PPARδ, PPARγ, AMPK, and Akt/PKB in C2C12 myoblasts. The expression of PPARδ, PPARγ, FATP, and GLUT4 was quantified using RT-qPCR and Western blot. α-amyrin increased these markers along with p-AMPK but not p-Akt/PKB. Molecular docking showed that α-amyrin acts as an AMPK-allosteric activator, and may be related to GLUT4 translocation, evidenced by confocal microscopy. These data support that α-amyrin could have an insulin-mimetic action in C2C12 myoblasts and should be considered as a bioactive molecule for new multitarget drugs with utility in T2D and other metabolic diseases.

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