Similar Datasets
Project description:In response to physical exercise and diet, skeletal muscle adapts to energetic demands through large transcriptional changes. This remodelling is associated with changes in skeletal muscle DNA methylation which may participate in the metabolic adaptation to extracellular stimuli. Yet, the mechanisms by which muscle-borne DNA methylation machinery responds to diet and exercise and impacts muscle function are unknown. Here, we investigated the function of de novo DNA methylation in fully differentiated skeletal muscle. We generated muscle-specific DNA methyltransferase 3A (DNMT3A) knockout mice (mD3AKO) and investigated the impact of DNMT3A ablation on skeletal muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3A reduced DNA methylation in skeletal muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation, but did not affect exercise capacity and whole-body energy metabolism compared to wild type mice. Loss of DNMT3A did not alter skeletal muscle mitochondrial function or the transcriptional response to exercise however did influence the expression of genes involved in muscle development. These data suggest that DNMT3A does not have a large role in the function of mature skeletal muscle although a role in muscle development and differentiation is likely.
| S-EPMC7875352 | biostudies-literature
Project description:Skeletal muscle can undergo large transcriptional changes in response to environmental stimuli such as diet or exercise in order to adapt to energetic demands. This remodelling has been associated with changes in muscle DNA methylation potentially regulating gene transcription. Despite abundant evidence that environmental stimuli can alter muscle DNA methylation, the mechanisms by which DNA methylation machinery respond to these stimuli and whether these have a physiological impact is still unclear. Therefore, we decided to investigate the importance of de novo DNA methylation on muscle methylation and function. We generated muscle specific DNMT3a knockout mice (mDKO) and investigated the impact of ablating DNMT3a in muscle on muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3a reduced DNA methylation in muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation. However, mDKO mice had a similar exercise capacity and whole-body energy metabolism as WT mice. Similarly, loss of DNMT3a did not alter muscle mitochondrial function or the transcriptional response to exercise however did increase the expression of genes involved in muscle development. These data suggest that DNMT3a does not have a large role in the function of mature muscle although a role in muscle development and differentiation is still likely.
2021-01-25 | GSE152348 | GEO
Project description:Skeletal muscle can undergo large transcriptional changes in response to environmental stimuli such as diet or exercise in order to adapt to energetic demands. This remodelling has been associated with changes in muscle DNA methylation potentially regulating gene transcription. Despite abundant evidence that environmental stimuli can alter muscle DNA methylation, the mechanisms by which DNA methylation machinery respond to these stimuli and whether these have a physiological impact is still unclear. Therefore, we decided to investigate the importance of de novo DNA methylation on muscle methylation and function. We generated muscle specific DNMT3a knockout mice (mDKO) and investigated the impact of ablating DNMT3a in muscle on muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3a reduced DNA methylation in muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation. However, mDKO mice had a similar exercise capacity and whole-body energy metabolism as WT mice. Similarly, loss of DNMT3a did not alter muscle mitochondrial function or the transcriptional response to exercise however did increase the expression of genes involved in muscle development. These data suggest that DNMT3a does not have a large role in the function of mature muscle although a role in muscle development and differentiation is still likely.
2021-01-25 | GSE152347 | GEO
Project description:Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity
| PRJNA639065 | ENA
Project description:Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity [RRBS]
| PRJNA639068 | ENA
Project description:Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity [RNA-seq]
| PRJNA639067 | ENA
Project description:The relationship between the age-associated decline in mitochondrial function and its effect on skeletal muscle physiology and function remain unclear. In the current study, we examined to what extent physical activity contributes to the decline in mitochondrial function and muscle health during aging and compared mitochondrial function in young and older adults, with similar habitual physical activity levels. We also studied exercise-trained older adults and physically impaired older adults. Aging was associated with a decline in mitochondrial capacity, exercise capacity and efficiency, gait stability, muscle function, and insulin sensitivity, even when maintaining an adequate daily physical activity level. Our data also suggest that a further increase in physical activity level, achieved through regular exercise training, can largely negate the effects of aging. Finally, mitochondrial capacity correlated with exercise efficiency and insulin sensitivity. Together, our data support a link between mitochondrial function and age-associated deterioration of skeletal muscle.
| S-EPMC8346468 | biostudies-literature
Project description:Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeletal muscle, we investigated their role in this tissue. In vivo and in vitro endospanin-2 triggers ERK phosphorylation in skeletal muscle through an autophagy-dependent pathway. Furthermore, endospanin-2, but not endospanin-1, overexpression decreases muscle mitochondrial ROS production, induces fast-to-slow fiber-type switch, increases skeletal muscle glycogen content, and improves glucose homeostasis, ultimately promoting running endurance capacity. In line, endospanin-2-/- mice display higher lipid peroxidation levels, increased mitochondrial ROS production under mitochondrial stress, decreased ERK phosphorylation, and reduced endurance capacity. In conclusion, our results identify endospanin-2 as a potentially novel player in skeletal muscle metabolism, plasticity, and function.
| S-EPMC6012521 | biostudies-literature
Project description:Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.
| S-EPMC2962629 | biostudies-literature
Project description:1. The intramuscular oxygen partial pressure (pO2) in human gastrocnemius muscle was monitored during exercise and compared with metabolite concentrations reflecting the energy and the redox state in the tissue. Ten normal subjects and ten patients with peripheral vascular occlusive disease were investigated. 2. In normal subjects the pO2 at the end of exercise was related to the intensity of the exercise, expressed as effect (J/s) per contraction. 3. In both patients and normal subject the pO2 was related to the [ATP]/[ADP] ratio, the [lactate/[pyruvate] ratio and the phosphocreatine concentration in the muscle tissue at rest and during exercise. 4. At each pO2 value, a lower [lactate/[pyruvate] ratio was found in the muscle tissue of the patients compared with that of normal subjects. This was interpreted as a beneficial effect of the higher oxidative-enzyme capacity in the muscle of the patients. 5. The results show the importance of pO2 for the regulation of the energy and the redox state of the tissue. During exercise the changes induced in pO2 and thus the energy state will stimulate the respiratory rate. This might be an important link in triggering the oxidative-enzyme capacity in response to physical training as well as in peripheral vascular occlusive disease.
| S-EPMC1163530 | biostudies-other