Dataset Information

Resting skeletal muscle reduces ATP turnover during hibernation

ABSTRACT: In mammals, loss of food intake and reduced mechanical loading/activity of skeletal muscles leads to a very rapid loss in mass and function. However, during hibernation in bears, despite spending months without feeding and with very modest muscle activity, only moderate muscle wasting is observed. Part of this tissue sparing is due to a highly reduced metabolic activity in almost all tissues, including skeletal muscle. Interestingly, myosin, one of the most abundant proteins in skeletal muscle, can have different metabolic activities in inactive muscle. Therefore, to evaluate the functional and metabolic alterations in hibernating muscles, we performed an analysis on a single muscle fiber level. Individual fibers were taken from biopsies of the same bears either during hibernation or during the active phase in the summer. We confirm that muscle fibers from hibernating bears show no loss of fiber size and a mild reduction in force generating capacity. However, ATPase activity of single muscle fibers taken from hibernating bears show a significant reduction in ATPase activity, which is due to a reduced ATP turnover by myosin. By performing a single fiber proteomics analysis, we could determine in a fiber type specific manner that muscle fibers undergo a major remodeling of their proteome. Both type 2A and type 1/2A mixed fibers show a marked reduction in mitochondrial proteins during hibernation, with a decrease in proteins linked to the TCA cycle and mitochondrial translation.

INSTRUMENT(S): timsTOF Pro 2

ORGANISM(S): Ursus Arctos (brown Bear) (grizzly Bear)

TISSUE(S): Muscle Fibre

SUBMITTER: Luisa Marie Schmidt

LAB HEAD: Bert Blaauw

PROVIDER: PXD050980 | Pride | 2024-12-06

REPOSITORIES: Pride

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			Action	DRS
	Blank01_S2-F12_9-23-2023_03-33-29_14833.d.zip	Other
	Blank02_S2-G12_9-23-2023_09-51-48_14849.d.zip	Other
	Blank03_S2-H12_9-23-2023_16-33-41_14866.d.zip	Other
	Blank04_S3-A12_9-23-2023_22-28-19_14881.d.zip	Other
	Blank05_S3-B12_9-24-2023_04-46-37_14897.d.zip	Other

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Project description:Hibernation is energy saving adaptation involving suppression of activity to survive in highly seasonal environments. Immobility and disuse generate muscle loss in most mammalian species. In contrast to other mammals, bears and ground squirrels demonstrate limited muscle atrophy over the physical inactivity of winter hibernation. This suggests that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional program underlying molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screening in hind limb muscles comparing hibernating and summer active black bears and arctic ground squirrels by the use of custom 9,600 probe cDNA microarrays. The molecular pathway analysis showed an elevated proportion of overexpressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during hibernation that implies induction of translation at different hibernation states. The induction of protein biosynthesis likely contributes to attenuation of disuse muscle atrophy through prolonged periods of immobility and starvation. This adaptive mechanism allows hibernating mammals to maintain full musculoskeletal function and preserve mobility during and immediately after hibernation, thus promoting survival. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction of multiply genes involved in oxidation reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation. Black bears sampled during winter hibernation were compared with the animals sampled during summer. Muscle tissue were hybridized on a custom 12,800 cDNA probe nylon membrane microarray platform . Six hibernating and six summer active bears were studied in the experiment.

Project description:Hibernation is energy saving adaptation involving suppression of activity to survive in highly seasonal environments. Immobility and disuse generate muscle loss in most mammalian species. In contrast to other mammals, bears and ground squirrels demonstrate limited muscle atrophy over the physical inactivity of winter hibernation. This suggests that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional program underlying molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screening in hind limb muscles comparing hibernating and summer active black bears and arctic ground squirrels by the use of custom 9,600 probe cDNA microarrays. The molecular pathway analysis showed an elevated proportion of overexpressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during hibernation that implies induction of translation at different hibernation states. The induction of protein biosynthesis likely contributes to attenuation of disuse muscle atrophy through prolonged periods of immobility and starvation. This adaptive mechanism allows hibernating mammals to maintain full musculoskeletal function and preserve mobility during and immediately after hibernation, thus promoting survival. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction of multiply genes involved in oxidation reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation. Arctic ground squirrels sampled during winter hibernation were compared with the animals sampled during summer. Muscle was hybridized on a custom 9,600 probes nylon membrane microarray platform. Ten in late torpor, four in early arousal, then in late arousal were studied in experiments.

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Resting skeletal muscle reduces ATP turnover during hibernation

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