The impact of endurance exercise on global and AMPK gene-specific DNA methylation

King-Himmelreich, Tanya S.; Schramm, Stefanie; Wolters, Miriam; Schmetzer, Julia; Möser, Christine V.; Knothe, Claudia; Resch, Eduard; Peil, Johannes; Geißlinger, Gerd; Niederberger, Ellen

doi:10.1016/j.bbrc.2016.04.078

Cited by 49 publications

(34 citation statements)

References 27 publications

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“…Increasing the intensity of physical activity also increases the AMP/ATP ratio in skeletal muscle (Wang et al, ; King‐Himmelreich et al, ). As the previously described contraction process takes places and the cellular energy demand increases, the use of phosphate groups from ATP increases the amount of ADP and AMP, thus increasing the AMP/ATP ratio.…”

Section: Mitochondriamentioning

confidence: 99%

The Role of Exercise and TFAM in Preventing Skeletal Muscle Atrophy

Theilen

Kunkel

Tyagi

2017

Journal Cellular Physiology

116

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Skeletal muscle atrophy is the consequence of protein degradation exceeding protein synthesis. This arises for a multitude of reasons including the unloading of muscle during microgravity, post-surgery bedrest, immobilization of a limb after injury, and overall disuse of the musculature. The development of therapies prior to skeletal muscle atrophy settings to diminish protein degradation is scarce. Mitochondrial dysfunction is associated with skeletal muscle atrophy and contributes to the induction of protein degradation and cell apoptosis through increased levels of ROS observed with the loss of organelle function. ROS binds mtDNA, leading to its degradation and decreasing functionality. Mitochondrial transcription factor A (TFAM) will bind and coat mtDNA, protecting it from ROS and degradation while increasing mitochondrial function. Exercise stimulates cell signaling pathways that converge on and increase PGC-1α, a well-known activator of the transcription of TFAM and mitochondrial biogenesis. Therefore, in the present review we are proposing, separately, exercise and TFAM treatments prior to atrophic settings (muscle unloading or disuse) alleviate skeletal muscle atrophy through enhanced mitochondrial adaptations and function. Additionally, we hypothesize the combination of exercise and TFAM leads to a synergistic effect in targeting mitochondrial function to prevent skeletal muscle atrophy.

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Section: Mitochondriamentioning

confidence: 99%

The Role of Exercise and TFAM in Preventing Skeletal Muscle Atrophy

Theilen

Kunkel

Tyagi

2017

Journal Cellular Physiology

116

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“…; King‐Himmelreich et al . ). DNA methylation suppresses gene expression by modulating transcriptional machinery access to chromatin or by recruiting methyl‐binding proteins (Cedar & Bergman, ).…”

Section: Introductionmentioning

confidence: 97%

One week, but not 12 hours, of cast immobilization alters promotor DNA methylation patterns in the nNOS gene in mouse skeletal muscle

Tobisawa

Ito

Sudo

et al. 2019

The Journal of Physiology

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Key points DNA methylation may play an important role in regulating gene expression in skeletal muscle to adapt to physical activity and inactivity. Neuronal nitric oxide synthase (nNOS) in skeletal muscle is a key regulator of skeletal muscle mass; however, it is unclear whether nNOS expression is regulated by DNA methylation. We found that 1 week of cast immobilization increased nNOS DNA methylation levels and downregulated nNOS gene expression in atrophic slow‐twitch soleus muscle from the mouse leg. These changes were not detected in non‐atrophic fast‐twitch extensor digitorum longus muscle. Twelve hours of cast immobilization decreased nNOS gene expression, whereas nNOS DNA methylation levels were unchanged, suggesting that downregulation of nNOS gene expression by short‐term muscle inactivity is independent of the DNA methylation pattern. These findings contribute to a better understanding of the maintenance of skeletal muscle mass and prevention of muscle atrophy by epigenetic mechanisms via the nNOS/NO pathway. Abstract DNA methylation is a mechanism that controls gene expression in skeletal muscle under various environmental stimuli, such as physical activity and inactivity. Neuronal nitric oxide synthase (nNOS) regulates muscle atrophy in skeletal muscle. However, the mechanisms regulating nNOS expression in atrophic muscle remain unclear. We hypothesized that nNOS expression in atrophic muscle is regulated by DNA methylation of the nNOS promotor in soleus (Sol; slow‐twitch fibre dominant) and extensor digitorum longus (EDL; fast‐twitch fibre dominant) muscles. One week of cast immobilization induced significant muscle atrophy in Sol but not in EDL. We showed that 1 week of cast immobilization increased nNOS DNA methylation levels in Sol, although only a minor change was detected in EDL. Consistent with the increased DNA methylation levels in atrophic Sol, the gene expression levels of total nNOS and nNOSµ (i.e. the major splicing variant of nNOS in skeletal muscle) decreased. The abundance of the nNOS protein and cell membrane (especially type IIa fibre) immunoreactivity also decreased in atrophic Sol. These changes were not observed in EDL after 1 week of cast immobilization. Furthermore, despite the lack of significant atrophy, 12 h of cast immobilization decreased gene expression levels of total nNOS and nNOSµ in Sol. However, no association was detected between nNOS DNA methylation and gene expression. The expression of the nNOSβ gene, another splicing variant of nNOS, in EDL was unchanged by cast immobilization, whereas its expression was not detected in Sol. We concluded that chronic adaptation of nNOS gene expression in cast immobilized muscle may involve nNOS DNA methylation.

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“…How such circulating factors might regulate epigenetic processes in response to exercise are only just emerging. However, other studies have noted altered DNA methylation in response to both endurance and resistance exercise in various blood cells (Denham et al 2016;King-Himmelreich et al 2016), further supporting the idea that circulating factors might be important. Interestingly, the genomic loci and genes regulated in blood cells by these different exercise modalities are divergent.…”

Section: Exercise-mediated Epigenetic Alterations In Other Tissuesmentioning

confidence: 72%

Exercise and the Skeletal Muscle Epigenome

McGee

Walder

2017

Cold Spring Harb Perspect Med

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An acute bout of exercise is sufficient to induce changes in skeletal muscle gene expression that are ultimately responsible for the adaptive responses to exercise. Although much research has described the intracellular signaling responses to exercise that are linked to transcriptional regulation, the epigenetic mechanisms involved are only just emerging. This review will provide an overview of epigenetic mechanisms and what is known in the context of exercise. Additionally, we will explore potential interactions between metabolism during exercise and epigenetic regulation, which serves as a framework for potential areas for future research. Finally, we will consider emerging opportunities to pharmacologically manipulate epigenetic regulators and mechanisms to induce aspects of the skeletal muscle exercise adaptive response for therapeutic intervention in various disease states.

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The impact of endurance exercise on global and AMPK gene-specific DNA methylation

Cited by 49 publications

References 27 publications

The Role of Exercise and TFAM in Preventing Skeletal Muscle Atrophy

The Role of Exercise and TFAM in Preventing Skeletal Muscle Atrophy

One week, but not 12 hours, of cast immobilization alters promotor DNA methylation patterns in the nNOS gene in mouse skeletal muscle

Exercise and the Skeletal Muscle Epigenome

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