Estrogen-Related Receptor-a Coordinates Transcriptional Programs Essential for Exercise Tolerance and Muscle Fitness
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE61712 | GEO | 2014/12/08
SECONDARY ACCESSION(S): PRJNA261941
REPOSITORIES: GEO
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Project description:The molecular mechanisms involved in the coordinate regulation of the metabolic and structural determinants of muscle endurance are still poorly characterized. To help elucidate the role of ERRa in this process, gene expression arrays were employed resulting in the identification of ERRa-dependent genes involved in metabolic processes, oxidative stress response, maintenance of muscle fiber integrity and neovascularization. Gastrocnemius (n=3) isolated from 2-3 month old WT and ERRa-null mice under pre-exercise (sedentary) and post-exercise (2 h following acute exhaustion on a treadmill) were used for gene expression studies using Affymetrix mouse 2.0 gene ST arrays.
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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.
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