Alterations in peroxisome proliferator-activated receptor mRNA expression in skeletal muscle after acute and repeated bouts of exercise

The purpose of this study was to investigate the acute messenger (mRNA) expression of the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) isoforms, insulin-like growth factor-1Ea (IGF-1Ea), and myostatin in response to 2 resistance exercise intensities. In a uniform-balanced, crossover design, 10 participants performed 2 separate testing sessions involving a lower body resistance exercise component consisting of a lower intensity (50% of 1-repetition maximum; 1RM) protocol and a higher intensity (80% of 1RM) protocol of equal volumes. Muscle samples were obtained at before exercise, 45 min, 3 h, 24 h, and 48 h postexercise. Resistance exercise did not alter total PGC-1α mRNA expression; however, distinct responses of each PGC-1α isoform were observed. The response of each isoform was consistent between sessions, suggesting no effect of resistance exercise intensity on the complex transcriptional expression of the PGC-1α gene. IGF-1Ea mRNA expression significantly increased following the higher intensity session compared with pre-exercise and the lower intensity session. Myostatin mRNA expression was significantly reduced compared with pre-exercise values at all time points with no difference between exercise intensity. Further research is needed to determine the effects of the various isoforms of PGC-1α in human skeletal muscle on the translational level as well as their relation to the expression of IGF-1 and myostatin.

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An Increase in Murine Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α (PGC-1α) mRNA in Response to Exercise Is Mediated by β-Adrenergic Receptor Activation

Endocrinology ◽

10.1210/en.2006-1646 ◽

2007 ◽

Vol 148 (7) ◽

pp. 3441-3448 ◽

Cited By ~ 125

Author(s):

Shinji Miura ◽

Kentaro Kawanaka ◽

Yuko Kai ◽

Mayumi Tamura ◽

Masahide Goto ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Adrenergic Receptor ◽

Ex Vivo ◽

Specific Inhibitor ◽

Receptor Activation ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Brown Adipose ◽

Exercise Induced

A single bout of exercise increases expression of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α mRNA, which may promote mitochondrial biogenesis in skeletal muscle. In brown adipose tissue, cold exposure up-regulates PGC-1α expression via adrenergic receptor (AR) activation. Because exercise also activates the sympathetic nervous system, we examined whether exercise-induced increase in PGC-1α mRNA expression in skeletal muscle was mediated via AR activation. In C57BL/6J mice, injection of the β2-AR agonist clenbuterol, but not α-, β1-, or β3-AR agonists, increased PGC-1α mRNA expression more than 30-fold in skeletal muscle. The clenbuterol-induced increase in PGC-1α mRNA expression in mice was inhibited by pretreatment with the β-AR antagonist propranolol. In ex vivo experiments, direct exposure of rat epitrochlearis to β2-AR agonist, but not α-, β1-, and β3-AR agonist, led to an increase in levels of PGC-1α mRNA. Injection of β2-AR agonist did not increase PGC-1α mRNA expression in β1-, β2-, and β3-AR knockout mice (β-less mice). PGC-1α mRNA in gastrocnemius was increased 3.5-fold in response to running on a treadmill for 45 min. The exercise-induced increase in PGC-1α mRNA was inhibited by approximately 70% by propranolol or the β2-AR-specific inhibitor ICI 118,551. The exercise-induced increase in PGC-1α mRNA in β-less mice was also 36% lower than that in wild-type mice. These data indicate that up-regulation of PGC-1α expression in skeletal muscle by exercise is mediated, at least in part, by β-ARs activation. Among ARs, β2-AR may mediate an increase in PGC-1α by exercise.

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The effects of obesity-associated insulin resistance on mRNA expression of peroxisome proliferator-activated receptor-γ target genes, in dogs

British Journal Of Nutrition ◽

10.1017/s000711450772514x ◽

2007 ◽

Vol 98 (3) ◽

pp. 497-503 ◽

Cited By ~ 33

Author(s):

Constance Gayet ◽

Veronique Leray ◽

Masayuki Saito ◽

Brigitte Siliart ◽

Patrick Nguyen

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Mrna Expression ◽

Target Genes ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Glucose And Lipid Metabolism ◽

Visceral Adipose

Visceral adipose tissue and skeletal muscle have central roles in determining whole-body insulin sensitivity. The peroxisome proliferator-activated receptor-γ (PPARγ) is a potential mediator of insulin sensitivity. It can directly modulate the expression of genes that are involved in glucose and lipid metabolism, including GLUT4, lipoprotein lipase (LPL) and adipocytokines (leptin and adiponectin). In this study, we aimed to determine the effects of obesity-associated insulin resistance on mRNA expression of PPARγ and its target genes. Dogs were studied when they were lean and at the end of an overfeeding period when they had reached a steady obese state. The use of a sensitive, real-time PCR assay allowed a relative quantification of mRNA expression for PPARγ, LPL, GLUT4, leptin and adiponectin, in adipose tissue and skeletal muscle. In visceral adipose tissue and/or skeletal muscle, mRNA expression of PPARγ, LPL and GLUT4 were at least 2-fold less in obese and insulin-resistant dogs compared with the same animals when they were lean and insulin-sensitive. The mRNA expression and plasma concentration of leptin was increased, whereas the plasma level and mRNA expression of adiponectin was decreased, by obesity. In adipose tissue, PPARγ expression was correlated with leptin and adiponectin. These findings, in an original model of obesity induced by a prolonged period of overfeeding, showed that insulin resistance is associated with a decrease in PPARγ mRNA expression that could dysregulate expression of several genes involved in glucose and lipid metabolism.

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Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting

Journal of Applied Physiology ◽

10.1152/japplphysiol.01318.2003 ◽

2004 ◽

Vol 96 (6) ◽

pp. 2082-2087 ◽

Cited By ~ 66

Author(s):

Lawrence L. Spriet ◽

Rebecca J. Tunstall ◽

Matthew J. Watt ◽

Kate A. Mehan ◽

Mark Hargreaves ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Pyruvate Dehydrogenase ◽

Human Skeletal Muscle ◽

Mrna Abundance ◽

Whole Body ◽

Peroxisome Proliferator ◽

Transcriptional Activators ◽

Subsequent Increase ◽

Peroxisome Proliferator Activated Receptor

Fasting forces adaptive changes in whole body and skeletal muscle metabolism that increase fat oxidation and decrease the oxidation of carbohydrate. We tested the hypothesis that 40 h of fasting would decrease pyruvate dehydrogenase (PDH) activity and increase PDH kinase (PDK) isoform mRNA expression in human skeletal muscle. The putative transcriptional activators of PDK isozymes, peroxisome proliferator-activated receptor-α (PPAR-α) protein, and forkhead homolog in rhabdomyosarcoma (FKHR) mRNA were also measured. Eleven healthy adults fasted after a standard meal (25% fat, 60% carbohydrate, 15% protein) with blood and skeletal muscle samples taken at 3, 15, and 40 h postprandial. Fasting increased plasma free fatty acid, glycerol, and β-hydroxybutyrate concentrations and decreased glucose and insulin concentrations. PDH activity decreased from 0.88 ± 0.11 mmol acetyl-CoA · min-1 · kg wet muscle wt-1 at 3 h to 0.62 ± 0.10 ( P = not significant) and 0.39 ± 0.06 ( P < 0.05) mmol · min-1 · kg wet mass-1 after 15 and 40 h of fasting. Although all four PDK isoforms were expressed in human skeletal muscle, PDK-2 and -4 mRNA were the most abundant. PDK-1 and -3 mRNA abundance was ∼1 and 15% of the PDK-2 and -4 levels, respectively. The 40-h fast had no effect on PDK-1, -2, and -3 mRNA expression. PDK-4 mRNA was significantly increased ∼3-fold after 15 h and ∼14-fold after 40 h of fasting. Skeletal muscle PPAR-α protein and FKHR mRNA abundance were unaffected by the fast. The results suggest that decreased PDH activation after 40 h of fasting may have been a function of the large increase in PDK-4 mRNA expression and possible subsequent increase in PDK protein and activity. The changes in PDK-4 expression and PDH activity did not coincide with increases in the transcriptional activators PPAR-α and FKHR.

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Developmental and Tissue-Specific Involvement of Peroxisome Proliferator-Activated Receptor-α in the Control of Mouse Uncoupling Protein-3 Gene Expression

Endocrinology ◽

10.1210/en.2006-0226 ◽

2006 ◽

Vol 147 (10) ◽

pp. 4695-4704 ◽

Cited By ~ 14

Author(s):

Neus Pedraza ◽

Meritxell Rosell ◽

Joan Villarroya ◽

Roser Iglesias ◽

Frank J. Gonzalez ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Fatty Acids ◽

Fatty Acid ◽

Mrna Expression ◽

Uncoupling Protein ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Ucp3 Gene ◽

Uncoupling Protein 3

Uncoupling protein-3 (UCP3) is a member of the mitochondrial carrier family expressed preferentially in skeletal muscle and heart. It appears to be involved in metabolic handling of fatty acids in a way that minimizes excessive production of reactive oxygen species. Fatty acids are powerful regulators of UCP3 gene transcription. We have found that the role of peroxisome proliferator-activated receptor-α (PPARα) on the control of UCP3 gene expression depends on the tissue and developmental stage. In adults, UCP3 mRNA expression is unaltered in skeletal muscle from PPARα-null mice both in basal conditions and under the stimulus of starvation. In contrast, UCP3 mRNA is down-regulated in adult heart both in fed and fasted PPARα-null mice. This occurs despite the increased levels of free fatty acids caused by fasting in PPARα-null mice. In neonates, PPARα-null mice show impaired UCP3 mRNA expression in skeletal muscle in response to milk intake, and this is not a result of reduced free fatty acid levels. The murine UCP3 promoter is activated by fatty acids through either PPARα or PPARδ but not by PPARγ or retinoid X receptor alone. PPARδ-dependent activation could be a potential compensatory mechanism to ensure appropriate expression of UCP3 gene in adult skeletal muscle in the absence of PPARα. However, among transcripts from other PPARα and PPARδ target genes, only those acutely induced by milk intake in wild-type neonates were altered in muscle or heart from PPARα-null neonates. Thus, PPARα-dependent regulation is required for appropriate gene regulation of UCP3 as part of the subset of fatty-acid-responsive genes in neonatal muscle and heart.

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Skeletal Muscle Angiopoietin-Like Protein 4 and Glucose Metabolism in Older Adults after Exercise and Weight Loss

Metabolites ◽

10.3390/metabo10090354 ◽

2020 ◽

Vol 10 (9) ◽

pp. 354 ◽

Cited By ~ 1

Author(s):

Guoyan Li ◽

Hefang Zhang ◽

Alice S. Ryan

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Mrna Expression ◽

Body Fat ◽

Vastus Lateralis ◽

Lipoprotein Metabolism ◽

Oral Glucose ◽

Vastus Lateralis Muscle ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor

Angiopoietin-like protein 4 (ANGPTL4) is an adipokine that plays an important role in energy homoeostasis and lipid and lipoprotein metabolism. This study was designed to determine the effect of an exercise plus weight loss intervention on ANGPTL4 expression and its relationship with metabolic health. Thirty-five obese sedentary men (n = 18) and postmenopausal women (n = 17), (X ± SEM, age: 61 ± 1 years, BMI: 31.3 ± 0.7 kg/m2, VO2max: 21.7 ± 0.9 L/kg/min) completed a 6 month program of 3×/week aerobic exercise and 1×/week dietary instruction to induce weight loss (AEX + WL). Participants underwent vastus lateralis muscle biopsies, a hyperinsulinemic–euglycemic clamp, oral glucose tolerance tests and body composition testing. Basal skeletal muscle ANGPTL4 mRNA was lower in men than women (p < 0.01). Peroxisome proliferator-activated receptor (PPAR) alpha (PPARα) mRNA expression was higher in men than women (p < 0.05). There were no significance changes in serum or skeletal muscle ANGPTL4 (basal or insulin-stimulated) or muscle PPARα mRNA expression after AEX + WL. Muscle mRNA ANGPTL4 is correlated with serum ANGPTL4 (r = 0.41, p < 0.05), body fat (r = 0.64, p < 0.0001), and glucose utilization (r = 0.38, p < 0.05). AEX + WL does not change basal or insulin-stimulated skeletal muscle ANGPTL4 mRNA expression, suggesting other factors contribute to improved insulin sensitivity after the loss of body fat and improved fitness.

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17beta-estradiol upregulates the expression of peroxisome proliferator-activated receptor alpha and lipid oxidative genes in skeletal muscle

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0310037 ◽

2003 ◽

Vol 31 (1) ◽

pp. 37-45 ◽

Cited By ~ 58

Author(s):

SE Campbell ◽

KA Mehan ◽

RJ Tunstall ◽

MA Febbraio ◽

D Cameron-Smith

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Protein Content ◽

Pyruvate Dehydrogenase Kinase ◽

Peroxisome Proliferator ◽

Sprague Dawley ◽

Peroxisome Proliferator Activated Receptor ◽

Skeletal Muscle Lipid ◽

Peroxisome Proliferator Activated Receptors ◽

Cpt I

This study examined the actions of 17beta-estradiol (E(2)) and progesterone on the regulation of the peroxisome proliferator-activated receptors (PPARalpha and PPARgamma) family of nuclear transcription factors and the mRNA abundance of key enzymes involved in fat oxidation, in skeletal muscle. Specifically, carnitine palmitoyltransferase I (CPT I), beta-3-hydroxyacyl CoA dehydrogenase (beta-HAD), and pyruvate dehydrogenase kinase 4 (PDK4) were examined. Sprague-Dawley rats were ovariectomized and treated with placebo (Ovx), E(2), progesterone, or both hormones in combination (E+P). Additionally, sham-operated rats were treated with placebo (Sham) to serve as controls. Hormone (or vehicle only) delivery was via time release pellets inserted at the time of surgery, 15 days prior to analysis. E(2) treatment increased PPARalpha mRNA expression and protein content (P<0.05), compared with Ovx treatment. E(2) also resulted in upregulated mRNA of CPT I and PDK4 (P<0.05). PPARgamma mRNA expression was also increased (P<0.05) by E(2) treatment, although protein content remained unaltered. These data demonstrate the novel regulation of E(2) on PPARalpha and genes encoding key proteins that are pivotal in regulating skeletal muscle lipid oxidative flux.

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

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2020-0030 ◽

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.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00380.2016 ◽

2017 ◽

Vol 312 (5) ◽

pp. E394-E406 ◽

Cited By ~ 10

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.

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