Methylome profiling of intrinsic aerobic capacity signatures in aged rat skeletal muscle
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE330608 | GEO | 2026/07/27
REPOSITORIES: GEO
Similar Datasets
Project description:Soleus muscle RNA-seq was performed in aged female selectively bred high-capacity runner (HCR) and low-capacity runner (LCR) rats to characterize baseline transcriptional differences associated with intrinsic aerobic capacity and exercise-associated transcriptional responses after voluntary wheel running.
2026-07-27 | GSE333619 | GEO
Project description:Epidemiological studies reveal a strong link between low aerobic capacity and metabolic and cardiovascular diseases. Two-way artificial selection of rats based on low and high intrinsic exercise capacity has produced two strains that also differ in risk for metabolic syndrome (Koch LG, Britton SL. Artificial selection for intrinsic aerobic endurance running capacity in rats. Physiol Genomics 5:45-52, 2001). Here we investigated skeletal muscle characteristics and genotype-phenotype relationships behind high and low inherited aerobic exercise capacity and the link between oxygen metabolism and metabolic disease risk factors in rats derived from generation 18. This population (n=24) of high capacity runners (HCR) and low capacity runners (LCR) differed by 615% in maximal treadmill running capacity. LCR were significantly significantly heavier and had increased blood glucose, serum insulin and triglyceride concentration. HCR had higher resting metabolic rate than LCR. Capillaries/mm2 and capillary-to-fiber ratio were significantly greater in HCR rats in soleus and gastrocnemius and capillary-to-fiber ratio in extensor digitorum longus (EDL) muscle. Subsarcolemmal mitochondrial area was 96% (p<0.01) and intermyofibrillar area was 32% (p<0.05) larger in HCR soleus. Microarray results showed that 126 genes were significantly up-regulated and 113 genes were down-regulated in HCR (p<0.05). Functional clustering and unbiased correlation analysis of muscle microarray data revealed that genes up-regulated in HCR were related to mitochondria, carboxylic acid and lipid metabolism, and oxidoreductase activity. In conclusion, our data show that aerobic capacity is strongly linked to the architecture of energy transfer and corroborate the importance of oxygen metabolism as the determinant of metabolic health and complex metabolic diseases such as metabolic syndrome and type 2 diabetes. Total RNA obtained from gastrocnemius muscle was compared between rat strains of low and high inherited aerobic exercise capacity.
2010-04-13 | E-GEOD-17190 | biostudies-arrayexpress
Project description:Epidemiological studies reveal a strong link between low aerobic capacity and metabolic and cardiovascular diseases. Two-way artificial selection of rats based on low and high intrinsic exercise capacity has produced two strains that also differ in risk for metabolic syndrome (Koch LG, Britton SL. Artificial selection for intrinsic aerobic endurance running capacity in rats. Physiol Genomics 5:45-52, 2001). Here we investigated skeletal muscle characteristics and genotype-phenotype relationships behind high and low inherited aerobic exercise capacity and the link between oxygen metabolism and metabolic disease risk factors in rats derived from generation 18. This population (n=24) of high capacity runners (HCR) and low capacity runners (LCR) differed by 615% in maximal treadmill running capacity. LCR were significantly significantly heavier and had increased blood glucose, serum insulin and triglyceride concentration. HCR had higher resting metabolic rate than LCR. Capillaries/mm2 and capillary-to-fiber ratio were significantly greater in HCR rats in soleus and gastrocnemius and capillary-to-fiber ratio in extensor digitorum longus (EDL) muscle. Subsarcolemmal mitochondrial area was 96% (p<0.01) and intermyofibrillar area was 32% (p<0.05) larger in HCR soleus. Microarray results showed that 126 genes were significantly up-regulated and 113 genes were down-regulated in HCR (p<0.05). Functional clustering and unbiased correlation analysis of muscle microarray data revealed that genes up-regulated in HCR were related to mitochondria, carboxylic acid and lipid metabolism, and oxidoreductase activity. In conclusion, our data show that aerobic capacity is strongly linked to the architecture of energy transfer and corroborate the importance of oxygen metabolism as the determinant of metabolic health and complex metabolic diseases such as metabolic syndrome and type 2 diabetes.
2010-04-01 | GSE17190 | GEO
Project description:Purpose: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and soleus gene expression we examined genome-wide gene expression in soleus muscle of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in man, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in the two groups, since accumulating evidence indicates that exercise has profound beneficial effects on the metabolic syndrome. Methods: Soleus gene expression of both sedentary and exercise trained HCR and LCR was characterized by microarray- and gene ontology analysis. Results: Although HCR and LCR had an inborn 347% difference in running capacity, only three genes were found differentially expressed in the soleus muscle between the two groups. Up-regulation of the mitochondrial enzyme leucyl-transferRNA synthetase (LARS2) was found in the sedentary LCR. Increased expression of LARS2 has been associated with a mitochondrial DNA mutation linked to maternally inherited diabetes and mitochondrial dysfunction. In line with our findings, a growing body of evidence suggests that LCR have compromised mitochondrial function. After exercise training, 58 genes were altered in the soleus muscle of HCR, in contrast to only one in the LCR group. This suggests that animals born with different levels of fitness respond different to the same type of exercise training. Adaptations to exercise in HCR seemed to be associated with increased lipid metabolism and fatty acid elongation in the mitochondria. Also, genes associated with the peroxisomes, seemed to be central in the adaptation to exercise. Conclusion: The results indicate that (i) LCR might have mitochondrial dysfunction, which may be a contributing factor of the low inborn aerobic capacity, (ii) animals born with different levels of fitness respond different to the same exercise program. Keywords: aerobic capacity, metabolic syndrome, soleus muscle, gene expression, metabolism
2008-06-01 | GSE10527 | GEO
Project description:Purpose: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and soleus gene expression we examined genome-wide gene expression in soleus muscle of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in man, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in the two groups, since accumulating evidence indicates that exercise has profound beneficial effects on the metabolic syndrome. Methods:; Soleus gene expression of both sedentary and exercise trained HCR and LCR was characterized by microarray- and gene ontology analysis. Results: Although HCR and LCR had an inborn 347% difference in running capacity, only three genes were found differentially expressed in the soleus muscle between the two groups. Up-regulation of the mitochondrial enzyme leucyl-transferRNA synthetase (LARS2) was found in the sedentary LCR. Increased expression of LARS2 has been associated with a mitochondrial DNA mutation linked to maternally inherited diabetes and mitochondrial dysfunction. In line with our findings, a growing body of evidence suggests that LCR have compromised mitochondrial function. After exercise training, 58 genes were altered in the soleus muscle of HCR, in contrast to only one in the LCR group. This suggests that animals born with different levels of fitness respond different to the same type of exercise training. Adaptations to exercise in HCR seemed to be associated with increased lipid metabolism and fatty acid elongation in the mitochondria. Also, genes associated with the peroxisomes, seemed to be central in the adaptation to exercise. Conclusion: The results indicate that (i) LCR might have mitochondrial dysfunction, which may be a contributing factor of the low inborn aerobic capacity, (ii) animals born with different levels of fitness respond different to the same exercise program. Experiment Overall Design: There are 16 samples in this study.
2008-06-18 | E-GEOD-10527 | biostudies-arrayexpress
Project description:Oxidative posttranslational modifications (Ox-PTMs) regulate cellular homeostasis in several tissues, including skeletal and cardiac muscles. The putative relationship between Ox-PTMs and intrinsic components of oxidative energy metabolism has not been previously described. We determined the metabolic phenotype and the Ox-PTM profile in the skeletal and cardiac muscles of rats selected for low (LCR) or high (HCR) intrinsic aerobic capacity. The HCR rats have a pronounced increase in mitochondrial content and antioxidant capacity when compared to LCR rats in the skeletal muscle, but only modest changes in the cardiac muscle. Redox proteomics analysis reveals that HCR and LCR rats have different Ox-PTM of cysteine (Cys) residue profile in the skeletal and cardiac muscles. HCR rats have higher number of oxidized Cys residues in the skeletal muscle and conversely display higher number of reduced Cys residues in the cardiac muscle than LCR rats. Most of the proteins with differentially oxidized Cys residues in the skeletal muscle are important regulators of the oxidative metabolism. The most significantly oxidized protein in the skeletal muscle of HCR rats is malate dehydrogenase (MDH1). Interestingly, HCR rats show higher MDH1 activity in the skeletal muscle, but not in the cardiac muscle. Thus, this study uncovers an association between Ox-PTMs and intrinsic aerobic capacity, providing new insights into the role of Ox-PTMs as essential signaling to maintain metabolic homeostasis in different muscle types.
2019-11-12 | PXD009109 | Pride
Project description:Low aerobic exercise capacity increases susceptibility to smoking-induced inflammation and tissue damage 38 animals total: 12 HCR Smoke, 12 LCR Smoke, 7 HCR sham, 7 LCR sham
2016-02-15 | E-GEOD-22456 | biostudies-arrayexpress
Project description:Aging is accompanied by progressive decline in brain function, and aerobic fitness is thought to influence brain health. To examine whether intrinsic exercise capacity is associated with a distinct brain molecular phenotype in aging, we profiled hippocampal DNA methylation by reduced representation bisulfite sequencing (RRBS) in aged selectively bred rats with high or low intrinsic aerobic capacity.
2026-07-12 | GSE328395 | GEO
Project description:Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high- and low running capacity (HCR and LCR, respectively) over 16 generations. HCR were born with an athletic phenotype, whereas LCR exhibited features of the metabolic syndrome. Left ventricle gene expression of both sedentary and exercise trained HCR and LCR was characterized by microarray- and gene ontology analysis. Western immunoblots and immunohistochemistry were used to validate the results at protein level. Out of 28.0000 screened genes, 1540 were differentially expressed between HCR and LCR. HCR expressed higher amounts of genes involved in lipid metabolism, whereas LCR expressed higher amounts of the genes involved in glucose metabolism and transport. By simply selecting for running capacity, we created a difference in cardiac energy substrate utilisation from normal mitochondrial fatty acid betaoxidation in HCR to carbohydrate metabolism in LCR. This event often occurs in diseased hearts. Differential expression of genes involved in cardiomyocyte growth was also found. LCR rats were associated with fetal gene expression, indicating the presence of pathological remodelling signaling. In addition, different expression of genes associated with cardiac contractility and cellular stress were detected. Also, hypoxia triggered transcription seemed to be involved in several of the functional differences between HCR and LCR. In conclusion, high- versus low aerobic capacity was associated with differences in genes regulating cardiac energy substrate, growth signalling, contractility and cellular stress. Keywords: metabolic syndrome analysis
2008-01-04 | GSE9445 | GEO
Project description:We used old (~96-102 weeks of age) and young (~28-34 weeks of age) rats from HCR and LCR generations 29 and 32, respectively. The study included eight groups; HCR-Old-Exhausted (H-O-E, n=6), HCR-Old-Rest (H-O-R, n=6), HCR-Young-Exhausted (H-Y-E, n=6), HCR- Young -Rest (H-Y-R, n=6), LCR-Old-Exhausted (L-O-E, n=6), LCR-Old-Rest (L-O-R, n=6), LCR-Young-Exhausted (L-Y-E, n=6), and LCR- Young -Rest (L-Y-R, n=6). For the exhausted rats, dissections were performed within 10 min after the maximal running distance was reached. We extracted skeletal muscle RNA from a total of 48 female animals (n=6 in each of the 8 group). Skeletal muscle tissue was obtained from the Extensor digitorum longus (EDL). All rats were dissected immediately after sacrificing, and all tissue samples were immediately weighed and snap frozen in liquid nitrogen, and stored at -80 ºC. Total RNA was extracted from frozen tissue with Trizol reagent (Invitrogen, Carlsbad, CA), treated with DNase-free (Invitrogen, Carlsbad, CA) and cleaned up with RNeasy columns (Qiagen, Hilden, Germany)
2015-12-03 | GSE75629 | GEO