Thiazolidinedione-induced activation of the transcription factor peroxisome proliferator-activated receptor γ in cells adjacent to the murine skeletal muscle: implications for fibroblast functions

1999 ◽  
Vol 439 (3) ◽  
pp. 288-296 ◽  
Author(s):  
B. Löhrke ◽  
S.K. Shahi ◽  
B. Krüger ◽  
P. Schmidt ◽  
U. Renne ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Murine Skeletal Muscle ◽  
In Cells

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.

Contractile activity-induced mitochondrial biogenesis and mTORC1

2012 ◽  
Vol 303 (5) ◽  
pp. C540-C547 ◽  
Author(s):  
Heather N. Carter ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Contractile Activity ◽  
Mammalian Target Of Rapamycin ◽  
Mitochondrial Proteins ◽  
Peroxisome Proliferator ◽  
Mitochondrial Content ◽  
Peroxisome Proliferator Activated Receptor ◽  
Murine Skeletal Muscle ◽  
Resting Muscle

In response to exercise training, or chronic contractile activity, mitochondrial content is known to be enriched within skeletal muscle. However, the molecular mechanisms that mediate this adaptation are incompletely defined. Recently, the protein complex, mammalian target of rapamycin complex 1 (mTORC1), has been identified to facilitate the expression of nuclear genes encoding mitochondrial proteins (NUGEMPs) in resting muscle cells via the interaction of the mTORC1 components, mTOR and raptor, the transcription factor Yin Yang 1, and peroxisome proliferator-activated receptor-γ coactivator-1α. It is currently unknown if this mechanism is operative during the increase in mitochondrial content that occurs within skeletal muscle with chronic contractile activity (CCA). Thus we employed a cell culture model of murine skeletal muscle and subjected the myotubes to CCA for 3 h per day for 4 consecutive days in the presence or absence of the mTORC1 inhibitor rapamycin. CCA produced increases in the mitochondrial markers cytochrome oxidase (COX) IV (2.5-fold), Tfam (1.5-fold), and COX activity (1.6-fold). Rapamycin-mediated inhibition of mTORC1 did not suppress these CCA-induced increases in mitochondrial proteins and organelle content. mTORC1 inhibition alone produced a selective upregulation of mitochondrial proteins (COX IV, Tfam), but diminished organelle state 3 respiration. CCA restored this impairment to normal. Our results suggest that mTORC1 activity is not integral for the increase in mitochondrial content elicited by CCA, but is required to maintain mitochondrial function and homeostasis in resting muscle.

scholarly journals Caffeine protects against stress-induced murine depression through activation of PPARγC1α-mediated restoration of the kynurenine pathway in the skeletal muscle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chongye Fang ◽  
Shuhei Hayashi ◽  
Xiaocui Du ◽  
Xianbin Cai ◽  
Bin Deng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Levels ◽  
Chronic Mild Stress ◽  
Kynurenine Pathway ◽  
Peroxisome Proliferator ◽  
Mild Stress ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intermediate Metabolites ◽  
Key Enzyme ◽  
Murine Skeletal Muscle

AbstractExercise prevents depression through peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α)-mediated activation of a particular branch of the kynurenine pathway. From kynurenine (KYN), two independent metabolic pathways produce neurofunctionally different metabolites, mainly in somatic organs: neurotoxic intermediate metabolites via main pathway and neuroprotective end product, kynurenic acid (KYNA) via the branch. Elevated levels of KYN have been found in patients with depression. Herein, we investigated whether and how caffeine prevents depression, focusing on the kynurenine pathway. Mice exposed to chronic mild stress (CMS) exhibited depressive-like behaviours with an increase and decrease in plasma levels of pro-neurotoxic KYN and neuroprotective KYNA, respectively. However, caffeine rescued CMS-exposed mice from depressive-like behaviours and restored the plasma levels of KYN and KYNA. Concomitantly, caffeine induced a key enzyme converting KYN into KYNA, namely kynurenine aminotransferase-1 (KAT1), in murine skeletal muscle. Upon caffeine stimulation murine myotubes exhibited KAT1 induction and its upstream PGC-1α sustainment. Furthermore, a proteasome inhibitor, but not translational inhibitor, impeded caffeine sustainment of PGC-1α, suggesting that caffeine induced KAT1 by inhibiting proteasomal degradation of PGC-1α. Thus, caffeine protection against CMS-induced depression may be associated with sustainment of PGC-1α levels and the resultant KAT1 induction in skeletal muscle, and thereby consumption of pro-neurotoxic KYN.

Influence of irisin on diet-induced metabolic syndrome in experimental rat model

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Dalia Medhat ◽  
Mona A. El-Bana ◽  
Sherien M. El-Daly ◽  
Magdi N. Ashour ◽  
Tahany R. Elias ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipid Profile ◽  
Histopathological Examination ◽  
Retinol Binding Protein ◽  
Albino Rats ◽  
Standard Diet ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Kidney Functions

Abstract Objective To evaluate the influence of irisin on the experimental paradigm of non-alcoholic fatty liver (NAFL) as a part of MetS cluster. Methods Forty male albino rats were divided into four groups; normal control, standard diet + irisin, high carbohydrate and fat diet (HCHF), and HCHF + irisin. After the experimental period, levels of fasting blood sugar (FBS), insulin, lipid profile, kidney functions, salusin-alpha (Sal-α), adropin, and retinol-binding protein-4 (RBP-4) were evaluated. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) expression in skeletal muscle was evaluated by quantitative real-time PCR. Aorta, liver, pancreas, and skeletal muscle tissue samples were prepared for histopathological examination. Results Rats administrated HCHF showed elevated levels of FBS, lipid profile, kidney functions, RBP-4, and downregulation of PGC-1α expression along with a decline in levels of insulin, Sal-α, and adropin while administration of irisin significantly attenuated these levels. Conclusions Irisin as based therapy could emerge as a new line of treatment against MetS and its related diseases.

scholarly journals Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice

2017 ◽  
Vol 312 (5) ◽  
pp. E394-E406 ◽  
Author(s):  
Samuel Lee ◽  
Teresa C. Leone ◽  
Lisa Rogosa ◽  
John Rumsey ◽  
Julio Ayala ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Early Stage ◽  
Peroxisome Proliferator ◽  
Disuse Atrophy ◽  
Proof Of Concept ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Disuse ◽  
Training Response

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy.

scholarly journals Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle

2015 ◽  
Vol 308 (9) ◽  
pp. C710-C719 ◽  
Author(s):  
Anna Vainshtein ◽  
Liam D. Tryon ◽  
Marion Pauly ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Acute Exercise ◽  
Transmembrane Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipid Trafficking ◽  
Mitochondrial Transcription Factor ◽  
Energy Demands ◽  
Niemann Pick ◽  
Exercise Induced

Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α. Anna Vainshtein received the AJP-Cell 2015 Paper of the Year award. Listen to a podcast with Anna Vainshtein and coauthor David A. Hood at http://ajpcell.podbean.com/e/ajp-cell-paper-of-the-year-2015-award-podcast/ .

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