Dataset Information

Multi-omics characterization of recurrent exertional rhabdomyolysis in Standardbred horses

ABSTRACT: During an episode of acute rhabdomyolysis, a microarray study identified differential expression of calcium-regulatory, mitochondrial and metabolic genes in gluteal muscle of Standardbreds. Whether this represents expression related to acute myodegeneration or a specific molecular signature of susceptibility to recurrent exertional rhabdomyolysis (RER) is currently unknown. We compared gluteal muscle histopathology, gene/protein expression and antioxidant concentrations between Standardbreds with a history of, but not currently experiencing rhabdomyolysis, and race-trained controls to derive a molecular susceptibility profile.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Equus Caballus (horse)

TISSUE(S): Gluteal Muscle

SUBMITTER: Stephanie Valberg

LAB HEAD: Stephanie Valberg

PROVIDER: PXD026121 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

Enriched Pathways of Calcium Regulation, Cellular/Oxidative Stress, Inflammation, and Cell Proliferation Characterize Gluteal Muscle of Standardbred Horses between Episodes of Recurrent Exertional Rhabdomyolysis.

Valberg Stephanie J SJ Velez-Irizarry Deborah D Williams Zoë J ZJ Henry Marisa L ML Iglewski Hailey H Herrick Keely K Fenger Clara C

Genes 20221014 10

Certain Standardbred racehorses develop recurrent exertional rhabdomyolysis (RER-STD) for unknown reasons. We compared gluteal muscle histopathology and gene/protein expression between Standardbreds with a history of, but not currently experiencing rhabdomyolysis (<i>N</i> = 9), and race-trained controls (<i>N</i> = 7). Eight RER-STD had a few mature fibers with small internalized myonuclei, one out of nine had histologic evidence of regeneration and zero out of nine degeneration. However, RER-S ...[more]

PMID: 36292738

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Project description:Skeletal muscle is the largest tissue in the body and mainly relies on mitochondrial oxidative metabolism for sustainable ATP production. Reduced oxygen availability, also known as hypoxia, can be caused by high altitude or pathology and impacts mitochondria. Whereas long-term hypoxia results in increased reliance on glycolysis, reduced fatty acid oxidation and a decreased skeletal muscle mass, the in vivo mechanisms of adaptation of skeletal muscle to acute hypoxia remain elusive. Therefore, we aimed to provide an integrated description of the response of the M. gastrocnemius to acute hypoxia. Fasted male C57BL/6JOlaHsd mice were exposed to 12% oxygen representing normobaric hypoxia versus 21% oxygen (normoxia) for six hours (n=12 mice per group). Whole-body energy metabolism and the transcriptome response of the M. gastrocnemius mice was analyzed and confirmed by acylcarnitine determination and RT-qPCR. On whole-body level, six hours of hypoxia reduced energy expenditure, increased blood glucose and tended to further decrease the respiratory exchange ratio (RER). Whole genome transcriptome analysis revealed upregulation of the FOXO signalling pathway including an increased expression of Trib3, which was positively correlated with blood glucose. Apart from upregulation of Cpt1a, which negatively correlated with the RER, and SLC25a25 (Cact), fatty acid β-oxidation was not regulated. Together with significantly increased muscle C14 and C16-acylcarnitines this supports no increased fatty acid catabolism in muscle. In addition, the hypoxia-induced FOXO activation could also be connected to altered gene profiles related to fiber type switching, extracellular matrix remodelling, muscle differentiation and the denervation of neuromuscular junctions (NMJ). Conclusively, our results suggest that an acute, six hours exposure of mice to hypoxia impacts M. gastrocnemius via FOXO1, initiating alterations in skeletal muscle that may ultimately contribute to tissue remodelling. This supports an early role of hypoxia in tissue alterations in hypoxia-associated conditions such as aging and obesity. The observed impact of hypoxia on denervated NMJ is novel and warrants further investigation.

Dataset Information

Multi-omics characterization of recurrent exertional rhabdomyolysis in Standardbred horses

Publications

Enriched Pathways of Calcium Regulation, Cellular/Oxidative Stress, Inflammation, and Cell Proliferation Characterize Gluteal Muscle of Standardbred Horses between Episodes of Recurrent Exertional Rhabdomyolysis.

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