The cell nuclei of skeletal muscle cells are transcriptionally active in hibernating edible dormice

Hibernating mammals conserve energy in the winter by undergoing prolonged bouts of torpor, interspersed with brief arousals back to euthermia. These bouts are accompanied by a suite of reversible physiological and biochemical changes; however, much remains to be discovered about the molecular mechanisms involved. Given the seasonal nature of hibernation, it stands to reason that underlying plastic epigenetic mechanisms should exist. One such form of epigenomic regulation involves the reversible modification of cytosine bases in DNA by methylation. DNA methylation is well known to be a mechanism that confers upon DNA its cellular identity during differentiation in response to innate developmental cues. However, it has recently been hypothesized that DNA methylation also acts as a mechanism for adapting genome function to changing external environmental and experiential signals over different time scales, including during adulthood. Here, we tested the hypothesis that DNA methylation is altered during hibernation in adult wild animals. This study evaluated global changes in DNA methylation in response to hibernation in the liver and skeletal muscle of thirteen-lined ground squirrels along with changes in expression of DNA methyltransferases (DNMT1/3B) and methyl binding domain proteins (MBDs). A reduction in global DNA methylation occurred in muscle during torpor phases whereas significant changes in DNMTs and MBDs were seen in both tissues. We also report dynamic changes in DNA methylation in the promoter of the myocyte enhancer factor 2C (mef2c) gene, a candidate regulator of metabolism in skeletal muscle. Taken together, these data show that genomic DNA methylation is dynamic across torporarousal bouts during winter hibernation, consistent with a role for this regulatory mechanism in contributing to the hibernation phenotype.

Section: Discussionmentioning

confidence: 99%

Dynamic changes in global and gene specific DNA methylation during hibernation in adult thirteen-lined ground squirrels,Ictidomys tridecemlineatus

Alvarado

Mak

Liu

et al. 2015

“…Here again, hibernation typically results in relatively minor changes in fiber CSA, with most studies showing a reduction of only 0-10% (mean change of −4.4% for type I fibers and −2.4% for type II fibers) associated with hibernation (Andres- Cotton and Harlow, 2010;Deveci and Egginton, 2002a;Gao et al, 2012;Hershey et al, 2008;Lee et al, 2008Lee et al, , 2010Malatesta et al, 2009;Tinker et al, 1998). However, at the extremes, a few studies have shown reductions in fiber CSA of between −30% and −55% (Agostini et al, 1991;Steffen et al, 1991).…”

Section: Morphological Changes During Hibernationmentioning

confidence: 99%

Skeletal muscle mass and composition during mammalian hibernation

Cotton

2016

Hibernation is characterized by prolonged periods of inactivity with concomitantly low nutrient intake, conditions that would typically result in muscle atrophy combined with a loss of oxidative fibers. Yet, hibernators consistently emerge from winter with very little atrophy, frequently accompanied by a slight shift in fiber ratios to more oxidative fiber types. Preservation of muscle morphology is combined with downregulation of glycolytic pathways and increased reliance on lipid metabolism instead. Furthermore, while rates of protein synthesis are reduced during hibernation, balance is maintained by correspondingly low rates of protein degradation. Proposed mechanisms include a number of signaling pathways and transcription factors that lead to increased oxidative fiber expression, enhanced protein synthesis and reduced protein degradation, ultimately resulting in minimal loss of skeletal muscle protein and oxidative capacity. The functional significance of these outcomes is maintenance of skeletal muscle strength and fatigue resistance, which enables hibernating animals to resume active behaviors such as predator avoidance, foraging and mating immediately following terminal arousal in the spring.

“…It has also been reported that follistatin increases satellite cell proliferation, possibly by blocking myostatin (Gilson et al, 2009). A recent study reported no change in muscle fibre shape and size or fibre type during hibernation (Malatesta et al, 2009). Furthermore, they also reported that nuclear and mitochondrial activity is maintained during deep torpor (measurement of one time point during hibernation).…”

Section: N E Brooks K H Myburgh and K B Storeymentioning

confidence: 99%

“…Despite long periods of inactivity, large hibernators such as bears appear to avoid protein loss and maintain muscle functional capacity (Harlow et al, 2001;Lohuis et al, 2007). This phenomenon is not peculiar to bears, as resistance to atrophy is also found in golden-mantled ground squirrels (Rourke et al, 2004a;Rourke et al, 2004b), dormice (Malatesta et al, 2009) and lower vertebrates such as turtles (McDonagh et al, 2004).…”

Section: Introductionmentioning

confidence: 94%

“…Myonuclei of hibernating dormice are not different from euthermic controls and apoptosis is not a feature (Malatesta et al, 2009). Therefore, the control of protein synthesis and degradation in hibernator muscles is likely pre-transcriptional at the level of cell signaling, via either activation of growth promoting pathways or suppression of catabolic processes.…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Myostatin levels in skeletal muscle of hibernating ground squirrels

Brooks

Myburgh

Storey

2011

SUMMARYMyostatin, a negative regulator of muscle mass, is elevated during disuse and starvation. Mammalian hibernation presents a unique scenario, where animals are hypocaloric and in torpor, but the extent of muscle protein loss is minimized. We hypothesized that myostatin expression, which is usually increased early in disuse and under hypocaloric conditions, could be suppressed in this unique model. Skeletal muscle was collected from thirteen-lined ground squirrels, Spermophilus tridecemlineatus, at six time points during hibernation: control euthermic (CON); entrance into hibernation (ENT), body temperature (T b ) falling; early hibernation (EHib), stable T b in torpor for 24h; late hibernation (LHib), stable T b in torpor for 3days; early arousal (EAr), T b rising; and arousal (AR), T b restored to 34-37°C for about 18h. There was no significant increase of myostatin during ENT, EHib or LHib. Unexpectedly, there were approximately sixfold increases in myostatin protein levels as squirrels arose from torpor. The elevation during EAr remained high in AR, which represented an interbout time period. Mechanisms that could release the suppression or promote increased levels of myostatin were assessed. SMAD2 and phosphorylated SMAD2 were increased during EHib, but only the phosphorylated SMAD2 during AR mirrored increases in myostatin. Follistatin, a negative regulator of myostatin, did not follow the same time course as myostatin or its signaling pathway, indicating more control of myostatin at the signaling level. However, SMAD7, an inhibitory SMAD, did not appear to play a significant role during deep hibernation. Hibernation is an excellent natural model to study factors involved in the endogenous intracellular mechanisms controlling myostatin.