Project description:Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality; yet some individuals are exercise resistant, and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease-risk, we used selective breeding for 15 generation to develop rat models of low- and high-aerobic response to training. Before exercise training, rats selected as low- and high-responders had similar exercise capacities. However, after 8-wks of treadmill training low-responders failed to improve their exercise capacity, while high-responders improved by 54%. Remarkably, low-responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise resistant phenotype segregates with disease risk. Low-responders had impaired exercise-induced angiogenes0is in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low-responders. Low-responders had increased stress/inflammatory signaling and altered TGFβ signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease.

2014-05-23 | GSE57880 | GEO

Resistance to aerobic exercise training causes metabolic dysfunction and reveals novel exercise-regulated signaling networks

Project description:Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality; yet some individuals are exercise resistant, and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease-risk, we used selective breeding for 15 generation to develop rat models of low- and high-aerobic response to training. Before exercise training, rats selected as low- and high-responders had similar exercise capacities. However, after 8-wks of treadmill training low-responders failed to improve their exercise capacity, while high-responders improved by 54%. Remarkably, low-responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise resistant phenotype segregates with disease risk. Low-responders had impaired exercise-induced angiogenes0is in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low-responders. Low-responders had increased stress/inflammatory signaling and altered TGFM-NM-2 signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease. Cardiac and skeletal muscle from 3 high and 3 low responder rats were examined for differential miRNA expression using Exiqon microarrays

2014-05-23 | E-GEOD-57880 | biostudies-arrayexpress

Voluntary exercise suppresses tumor growth through exercise-directed recruitment and intratumoral infiltration of NK cells

Project description:Voluntary exercise reduces the risk of cancer and lowers the risk of disease recurrence. Yet the mechanisms for this protection remain to be elucidated. Here we demonstrate that exercise halves tumor growth through an exercise-dependent mobilization and intratumoral infiltration of NK cells in malignant melanoma. Using voluntary wheel running, we show that exercise prior to and during B16 tumor challenge reduced tumor growth by 67%, and this reduction was associated with increased inflammation and immune cell infiltrates, especially NK cells, in the tumors from exercising mice. Depletion of NK cells blunted the exercise-dependent reduction in tumor growth. Moreover, during exercise, NK cells were engaged through an epinephrine-dependent mobilization to the circulation and redistributed to peripheral tissues through an IL-6 dependent mechanism. This study highlights the importance of exercise-dependent immune regulation in the control of malignant melanoma Gene expression profile of melanoma tumor tissue from two groups of exercise and non-exercise mice

2016-07-21 | E-GEOD-62628 | biostudies-arrayexpress

High and low exercise responders

Project description:Aerobic exercise capacity is a strong predictor of disease and survivability but the utility of exercise intervention is largely dependent on how one’s genome interacts with an exercise-training environment. A newly developed rat model selectively bred for inherited differences in response to aerobic exercise training shows to be a useful resource to sort out the networks of genes responsible for signalling exercise-induced changes that benefit cardiac function.

2012-01-01 | GSE20997 | GEO

Dynamics of the human skeletal muscle transcriptome in response to exercise training - part 1

Project description:A total of 23 participants (data available in present submission and in GSE58608) completed three months of supervised aerobic exercise training of one leg. Skeletal muscle biopsies have been collected before and after the training period. We have investigated differences between trained and untrained leg and before and after training by studying the gene and isoform expression. Additional samples present in this study has been previously published (GEO accession number GSE58608). Analysis of transcriptome in skeletal muscle biopsy samples in response to exercise training in 22 participants (of the total 23 participants). One biopsy is collected from each leg before and after training period.

2015-01-21 | E-GEOD-60590 | biostudies-arrayexpress

Dynamics of the human skeletal muscle transcriptome in response to exercise training - part 1

2015-01-21 | GSE60590 | GEO

Voluntary exercise suppresses tumor growth through exercise-directed recruitment and intratumoral infiltration of NK cells

2016-07-21 | GSE62628 | GEO