Local cryotherapy minimally impacts the metabolome and transcriptome of human skeletal muscle

Sarver, Dylan C.; Sugg, Kristoffer B.; Disser, Nathaniel P; Enselman, Elizabeth R. Sibilsky; Awan, Tariq M; Mendias, Christopher L.

doi:10.1038/s41598-017-02754-5

Cited by 23 publications

(19 citation statements)

References 43 publications

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“…Lipidomics and metabolomics. The University of Michigan Metabolomics Core performed mass spectrometry based shotgun lipidomics and metabolomics measurements from snap frozen, homogenized muscle samples as described (18,19). For lipidomics, lipids were extracted from samples with a solvent mixture consisting of 2:2:2 (v/v/v) methanol:dichloromethane:water mixture at room temperature after adding internal standard mixture.…”

Section: Electron Microscopymentioning

confidence: 99%

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

Gumucio

Qasawa

Ferrara

et al. 2018

Preprint

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Myosteatosis is the pathological accumulation of lipid that can occur in conjunction with atrophy and fibrosis following skeletal muscle injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many clinical studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our objective was to determine the pathological changes that result in lipid accumulation in injured muscle fibers. We used a rat model of rotator cuff injury in this study, as the rotator cuff muscle group is particularly prone to the development of myosteatosis after injury. Muscles were collected from uninjured controls, or 10, 30, or 60 days after injury, and analyzed using a combination of muscle fiber contractility assessments, RNA sequencing, and undirected metabolomics, lipidomics and proteomics, along with bioinformatics techniques, to identify potential pathways and cellular processes that are dysregulated after rotator cuff tear. Bioinformatics analyses indicated that mitochondrial function was likely disrupted after injury. Based on these findings, and given the role that mitochondria play in lipid metabolism, we then performed targeted biochemical and imaging studies and determined that mitochondrial dysfunction and reduced fatty acid oxidation likely leads to the accumulation of lipid in myosteatosis.

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Section: Electron Microscopymentioning

confidence: 99%

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

Gumucio

Qasawa

Ferrara

et al. 2018

Preprint

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“…Mass spectrometry‐based metabolomics and lipidomics was performed by the University of Michigan Metabolomics Core as described . The summary data is provided in the manuscript, with complete data available in Supplementary Tables S1 and S2.…”

Section: Methodsmentioning

confidence: 99%

“…Mass spectrometry-based metabolomics and lipidomics was performed by the University of Michigan Metabolomics Core as described. 20,30 The summary data is provided in the manuscript, with complete data available in Supplementary Tables S1 and S2. The metabolites were extracted from frozen muscle, derivatized, and analyzed with gas chromatography-MS. 31 The quantification of metabolites was performed using JOURNAL OF ORTHOPAEDIC RESEARCH ® APRIL 2020 812 TALAREK ET AL.…”

Section: Metabolomics and Lipidomicsmentioning

confidence: 99%

The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy and Weakness After Rotator Cuff Tear

Talarek

Piacentini

Konja

et al. 2019

Journal Orthopaedic Research

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Chronic rotator cuff tears are a common source of shoulder pain and disability. Patients with rotator cuff tears often have substantial weakness, fibrosis, and fat accumulation, which limit successful surgical repair and postoperative rehabilitation. The Murphy Roths Large (MRL) strain of mice have demonstrated superior healing and protection against pathological changes in several disease and injury conditions. We tested the hypothesis that, compared with the commonly used C57Bl/6 (B6) strain, MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear. Adult male B6 and MRL mice were subjected to a rotator cuff tear, and changes in muscle fiber contractility and histology were measured. RNA sequencing and shotgun metabolomics and lipidomics were also performed. The muscles were harvested one month after tear. B6 and MRL mice had a 40% reduction in relative muscle force production after rotator cuff tear. RNA sequencing identified an increase in fibrosis‐associated genes and a reduction in mitochondrial metabolism genes. The markers of glycolytic metabolism increased in B6 mice, while MRL mice appeared to increase amino acid metabolism after tear. There was an accumulation of lipid after injury, although there was a divergent response between B6 and MRL mice in the types of lipid species that accrued. There were strain‐specific differences between the transcriptome, metabolome, and lipidome of B6 and MRL mice, but these differences did not protect MRL mice from weakness and pathological changes after rotator cuff tear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:811‐822, 2020

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“…performed mass spectrometry-based shotgun lipidomics and metabolomics measurements from snap frozen, homogenized muscle samples as described (14,41). For lipidomics, lipids were extracted from samples with a solvent mixture consisting of 2:2:2 (v/v/v) methanol:dichloromethane:water mixture at room temperature after adding internal standard mixture.…”

Section: Metabolomics and Lipidomics The University Of Michigan Metamentioning

confidence: 99%

Multiomics Analysis of the mdx/mTR Mouse Model of Duchenne Muscular Dystrophy

Pelt

Kharaz

Sarver

et al. 2019

Preprint

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Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease characterized by extensive muscle weakness. Patients with DMD lack a functional dystrophin protein, which transmits force and organizes the cytoskeleton of skeletal muscle. Multiomic studies evaluate combined changes in the transcriptome, proteome, and metabolome, and have been proposed as a way to obtain novel insight about disease processes from preclinical models.We therefore sought to use this approach to study pathological changes in dystrophic muscles.We evaluated hindlimb muscles of male mdx/mTR mice, which lack a functional dystrophin protein and have deficits in satellite cell abundance and proliferative capacity. Wild type (WT) C57BL/6J mice served as controls. Muscle fiber contractility was measured, along with changes in the transcriptome using RNA sequencing, and in the proteome, metabolome, and lipidome using mass spectroscopy. While mdx/mTR mice displayed gross pathological changes and continued cycles of degeneration and regeneration, we found no differences in fiber contractility between strains. However, there were numerous changes in the transcriptome and proteome related to protein balance, contractile elements, extracellular matrix, and metabolism. There was only a 53% agreement in fold change data between the proteome and transcriptome, highlighting the need to study protein abundance along with gene expression measures. Numerous changes in markers of skeletal muscle metabolism were observed, with dystrophic muscles exhibiting elevated glycolytic metabolites. These findings highlight the utility of multiomics in studying muscle disease, and provide additional insight into the pathological changes in dystrophic muscles that might help to guide evidence-based exercise prescription in DMD patients.

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Local cryotherapy minimally impacts the metabolome and transcriptome of human skeletal muscle

Cited by 23 publications

References 43 publications

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy and Weakness After Rotator Cuff Tear

Multiomics Analysis of the mdx/mTR Mouse Model of Duchenne Muscular Dystrophy

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