Skeletal muscle proteomics: carbohydrate metabolism oscillates with seasonal and torpor-arousal physiology of hibernation

Bone mass and skeletal muscle mass are controlled by factors such as genetics, diet and nutrition, growth factors and mechanical stimuli. Whereas increased mechanical loading of the musculoskeletal system stimulates an increase in the mass and strength of skeletal muscle and bone, reduced mechanical loading and disuse rapidly promote a decrease in musculoskeletal mass, strength and ultimately performance (i.e. muscle atrophy and osteoporosis). In stark contrast to artificially immobilised laboratory mammals, animals that experience natural, prolonged bouts of disuse and reduced mechanical loading, such as hibernating mammals and aestivating frogs, consistently exhibit limited or no change in musculoskeletal performance. What factors modulate skeletal muscle and bone mass, and what physiological and molecular mechanisms protect against losses of muscle and bone during dormancy and following arousal? Understanding the events that occur in different organisms that undergo natural periods of prolonged disuse and suffer negligible musculoskeletal deterioration could not only reveal novel regulatory factors but also might lead to new therapeutic options. Here, we review recent work from a diverse array of species that has revealed novel information regarding physiological and molecular mechanisms that dormant animals may use to conserve musculoskeletal mass despite prolonged inactivity. By highlighting some of the differences and similarities in musculoskeletal biology between vertebrates that experience disparate modes of dormancy, it is hoped that this Review will stimulate new insights and ideas for future studies regarding the regulation of atrophy and osteoporosis in both natural and clinical models of muscle and bone disuse.

Section: Discussionmentioning

confidence: 94%

Prevention of muscle wasting and osteoporosis: the value of examining novel animal models

Reilly

Franklin

2016

“…Coupled with a strong retention of type I fibers is a preference for fatty acids as a fuel source over carbohydrates (Buck and Barnes, 2000;Hindle et al, 2011). This alteration is accompanied by a decrease in activity and/or concentration of phosphofructokinase (MacDonald and Storey, 2005), fructose 1,6-bisphosphate aldolase (MacDonald and Storey, 2002) and glyceraldehyde 3-phosphate dehydrogenase (Soukri et al, 1995(Soukri et al, , 1996 during deep torpor.…”

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.

Section: Mechanisms Of Metabolic Suppressionmentioning

confidence: 99%

“…Enzymes that covalently modify other enzymes, for example by phosphorylation or acetylation, could account for this pattern. Indeed, muscle phosphoglucomutase, a cytosolic enzyme, is differentially phosphorylated among hibernation states (Hindle et al, 2011).Within mitochondria, soluble adenylate cyclase (sAC) can be activated by changes in the content of ATP, Ca 2+ and HCO 3 -(Valsecchi et al, 2013). Activation of sAC would stimulate intramitochondrial protein kinase A (PKA) (Schwoch et al, 1990), which can phosphorylate many ETS proteins (Valsecchi et al, 2013), altering their activity (Lee et al, 2005;Tomitsuka et al, 2009;Phillips et al, 2012).…”

mentioning

confidence: 99%

Metabolic suppression in mammalian hibernation: the role of mitochondria

Staples

2014

Hibernation evolved in some small mammals that live in cold environments, presumably to conserve energy when food supplies are low. Throughout the winter, hibernators cycle spontaneously between torpor, with low metabolism and near-freezing body temperatures, and euthermia, with high metabolism and body temperatures near 37°C. Understanding the mechanisms underlying this natural model of extreme metabolic plasticity is important for fundamental and applied science. During entrance into torpor, reductions in metabolic rate begin before body temperatures fall, even when thermogenesis is not active, suggesting active mechanisms of metabolic suppression, rather than passive thermal effects. Mitochondrial respiration is suppressed during torpor, especially when measured in liver mitochondria fuelled with succinate at 37°C in vitro. This suppression of mitochondrial metabolism appears to be invoked quickly during entrance into torpor when body temperature is high, but is reversed slowly during arousal when body temperature is low. This pattern may reflect body temperaturesensitive, enzyme-mediated post-translational modifications of oxidative phosphorylation complexes, for instance by phosphorylation or acetylation.KEY WORDS: Heat, Body temperature, Thermoregulation, Thermogenesis, Oxidative phosphorylation, Post-translational modification, Acetylation, Phosphorylation IntroductionMost mammals are strict endotherms, i.e. they maintain fairly constant body temperatures (T b ) near 37°C using heat derived primarily from endogenous metabolism. In cold environments, mammals retain some of this heat by regulating insulation (using underfur and/or subcutaneous fat), peripheral blood circulation (using vasoconstriction and/or countercurrent heat exchangers) and ventilatory evaporation. At very cold temperatures, the high gradient between T b and ambient temperature (T a ) causes large heat loss by radiation and conduction, which is also affected by convection of water or air. For small mammals, the high body surface area, relative to volume, results in greater mass-specific rates of heat loss. While large land mammals can increase insulation by changing the quality (microstructure) and quantity (length, density) of underfur, this option is limited for small mammals. Imagine a 70 mm long lemming growing fur 100 mm long; it might stay warm, but when it tripped over that fur it would be easy prey.Despite the challenges, many small mammals thrive in cold environments. To compensate for high heat loss, these mammals upregulate their capacities to produce metabolic heat. Though COMMENTARY Department of Biology, University of Western Ontario, London, ON, Canada, N6A 5B8.*Author for correspondence (jfstaple@uwo.ca) effective, this strategy requires large quantities of fuel during winter when food availability is typically low. Many small mammals use stored food to power thermogenic metabolism. For example, American red squirrels (Tamiascurius hudsonicus) cache spruce cones and feed on the seeds throughout winter, allowing th...