Exercise training impacts skeletal muscle gene expression related to the kynurenine pathway

Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence tryptophan metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults, whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Although exercise training has been shown to improve skeletal muscle mass in older adults, whether this also translates into improvements in transcription factors and metabolites related to the kynurenine pathway has yet to be examined. The aim of the present study was to examine the influence of a 12-wk exercise program on skeletal muscle gene expression of transcription factors, kynurenine aminotransferase (KAT) gene expression, and plasma concentrations of tryptophan metabolites (kynurenines) in healthy older men over 65 yr of age. Exercise training significantly increased skeletal muscle gene expression of transcription factors (peroxisome proliferator-activated receptor-γ coactivator 1α, peroxisome proliferator-activated receptor-α, and peroxisome proliferator-activated receptor-δ: 1.77, 1.99, 2.18-fold increases, respectively, P < 0.01] and KAT isoforms 1–4 (6.5, 2.1, 2.2, and 2.6-fold increases, respectively, P ≤ 0.01). Concentrations of plasma kynurenines were not altered. These results demonstrate that 12 wk of exercise training significantly altered skeletal muscle gene expression of transcription factors and gene expression related to the kynurenine pathway, but not circulating kynurenine metabolites in older men. These findings warrant future research to determine whether distinct exercise modalities or varying intensities could induce a shift in the kynurenine pathway in depressed older adults.

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Nitrate and Nitrite Treatment Modulate Performance and Available Fuel Sources In Zebrafish Muscle and Liver

Current Developments in Nutrition ◽

10.1093/cdn/nzaa066_013 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1758-1758

Author(s):

Rosa Keller ◽

Laura Beaver ◽

Patrick Reardon ◽

Norman Hord

Keyword(s):

Skeletal Muscle ◽

Exercise Performance ◽

Creatine Phosphate ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Muscle Gene Expression ◽

Nitrate Treatment ◽

Muscle Gene ◽

Nitrate And Nitrite

Abstract Objectives Treatment with nitrate, but not nitrite, improves exercise performance but the mechanisms responsible are not fully understood. Thus, we tested the hypothesis that nitrate and nitrite treatment alter exercise performance through regulation of genes related to glucose and lipid metabolism in skeletal muscle and liver. Furthermore, we tested the hypothesis that nitrate treatment caused increased abundance and utilization of metabolic fuels in muscle that require less oxygen for energy production. Methods Adult zebrafish fish were exposed to sodium nitrate (606.9 mg NaNO3/L water), sodium nitrite (19.5 mg NaNO2/L of water), or control water for 21 days (n = 9–12/treatment). Liver and muscle gene expression were analyzed by quantitative real-time PCR and liver and muscle metabolomes were assessed by 1H-NMR untargeted metabolomics. Results Nitrite treatment significantly increased carnitine palmitoyl transferase 1b (cpt1b) expression in the liver and significantly decreased acetyl-CoA carboxylase (acaca) expression in skeletal muscle. Nitrate treatment significantly increased expression of peroxisome proliferator activated receptor-γ (pparg) muscle while acaca significantly decreased in skeletal muscle. Nitrate treatment also induced significant increases in metabolic fuels, such as ATP and creatine phosphate, and fuel sources including β-hydroxybutyrate and glycolytic intermediates in rested skeletal muscle. After a graded exercise test, these metabolites decreased in skeletal muscle of nitrate-treated fish while they increased with exercise in the skeletal muscle of control-treated zebrafish. Conclusions Our data are consistent with the hypothesis that nitrate treatment altered lipid and carbohydrate metabolism of zebrafish, in part, through a pparg mediated mechanism in the liver, and may improve exercise performance through utilization of fuel sources that require less oxygen during exercise. In contrast, our data indicate that nitrite may attenuate exercise performance, in part, by promoting dependence on fatty acid oxidation in the liver of zebrafish. These mechanisms may mediate improved exercise tolerance in populations with cardiovascular disease. Funding Sources Celia Strickland and G. Kenneth Austin III Endowment and National Institutes of Health.

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Rosiglitazone-Mediated Effects on Skeletal Muscle Gene Expression Correlate with Improvements in Insulin Sensitivity in Individuals with HIV-Insulin Resistance

Pathology Research International ◽

10.4061/2011/736425 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8

Author(s):

Dennis C. Mynarcik ◽

Margaret A. McNurlan ◽

Mark M. Melendez ◽

James A. Vosswinkel ◽

Marie C. Gelato

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Insulin Sensitivity ◽

Muscle Tissue ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Muscle Gene Expression ◽

Mediated Effects ◽

Highly Correlated ◽

Muscle Gene

Rosiglitazone, an agonist of peroxisome proliferator activated receptor (PPARγ), improves insulin sensitivity by increasing insulin-stimulated glucose uptake into muscle tissue. This study was undertaken to assess changes in expression of PPAR-regulated genes in muscle tissue following treatment of HIV-associated insulin resistance with rosiglitazone. Muscle gene expression was assessed in twenty-two seronegative HIV subjects (control), 21 HIV-infected individuals with normal insulin sensitivity (HIV-IS) and 19 HIV-infected individuals with insulin resistance (HIV-IR). A subset of the HIV-IR group (N=10) were re-evaluated 12 weeks after treatment with 8 mg/d of rosiglitazone. The HIV-IR group's rosiglitazone-mediated improvement in insulin sensitivity was highly correlated with increased expression of PPARγ and carnitine palmitoyl transferase-1 (CPT-1), (r=0.87, P<.001) and (r=0.95, P<.001), respectively. The changes in PPARγ expression were also correlated with the changes in CPT1 expression (r=0.75, P=.009). The results suggest that rosiglitazone; may have a direct effect on muscle tissue to improve insulin sensitivity.

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Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max

Physiological Genomics ◽

10.1152/physiolgenomics.90282.2008 ◽

2008 ◽

Vol 35 (3) ◽

pp. 213-221 ◽

Cited By ~ 19

Author(s):

Anja Bye ◽

Morten A. Høydal ◽

Daniele Catalucci ◽

Mette Langaas ◽

Ole Johan Kemi ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Metabolic Syndrome ◽

Exercise Training ◽

Soleus Muscle ◽

Strong Predictor ◽

Muscle Gene Expression ◽

The Metabolic Syndrome ◽

Muscle Gene ◽

The Relationship

The relationship between inborn maximal oxygen uptake (VO2max) and skeletal muscle gene expression is unknown. Since low VO2max is a strong predictor of cardiovascular mortality, genes related to low VO2max might also be involved in cardiovascular disease. To establish the relationship between inborn VO2max and gene expression, we performed microarray analysis of the soleus muscle of rats artificially selected for high- and low running capacity (HCR and LCR, respectively). In LCR, a low VO2max was accompanied by aggregation of cardiovascular risk factors similar to the metabolic syndrome. Although sedentary HCR were able to maintain a 120% higher running speed at VO2max than sedentary LCR, only three transcripts were differentially expressed (FDR ≤ 0.05) between the groups. Sedentary LCR expressed high levels of a transcript with strong homology to human leucyl-transfer RNA synthetase, of whose overexpression has been associated with a mutation linked to mitochondrial dysfunction. Moreover, we studied exercise-induced alterations in soleus gene expression, since accumulating evidence indicates that long-term endurance training has beneficial effects on the metabolic syndrome. In terms of gene expression, the response to exercise training was more pronounced in HCR than LCR. HCR upregulated several genes associated with lipid metabolism and fatty acid elongation, whereas LCR upregulated only one transcript after exercise training. The results indicate only minor differences in soleus muscle gene expression between sedentary HCR and LCR. However, the inborn level of fitness seems to influence the transcriptional adaption to exercise, as more genes were upregulated after exercise training in HCR than LCR.

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Energy sensing and regulation of gene expression in skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01126.2005 ◽

2007 ◽

Vol 102 (2) ◽

pp. 529-540 ◽

Cited By ~ 52

Author(s):

Damien Freyssenet

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Energy Homeostasis ◽

Regulation Of Gene Expression ◽

Hypoxia Inducible Factor ◽

Peroxisome Proliferator ◽

Muscle Plasticity ◽

Muscle Gene Expression ◽

Energy Sensing ◽

Muscle Gene

Major modifications in energy homeostasis occur in skeletal muscle during exercise. Emerging evidence suggests that changes in energy homeostasis take part in the regulation of gene expression and contribute to muscle plasticity. A number of energy-sensing molecules have been shown to sense variations in energy homeostasis and trigger regulation of gene expression. The AMP-activated protein kinase, hypoxia-inducible factor 1, peroxisome proliferator-activated receptors, and Sirt1 proteins all contribute to altering skeletal muscle gene expression by sensing changes in the concentrations of AMP, molecular oxygen, intracellular free fatty acids, and NAD+, respectively. These molecules may therefore sense information relating to the intensity, duration, and frequency of muscle exercise. Mitochondria also contribute to the overall response, both by modulating the response of energy-sensing molecules and by generating their own signals. This review seeks to examine our current understanding of the roles that energy-sensing molecules and mitochondria can play in the regulation of gene expression in skeletal muscle.

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Pharmacological regulation of skeletal muscle gene expression

Nuclear Receptor Signaling Atlas Datasets ◽

10.1621/datasets.05002 ◽

2013 ◽

Author(s):

R Evans

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Muscle Gene Expression ◽

Pharmacological Regulation ◽

Muscle Gene

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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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