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Effects of endurance training on skeletal muscle mitochondrial function in Huntington disease patients.

ABSTRACT: Mitochondrial dysfunction may represent a pathogenic factor in Huntington disease (HD). Physical exercise leads to enhanced mitochondrial function in healthy participants. However, data on effects of physical exercise on HD skeletal muscle remains scarce. We aimed at investigating adaptations of the skeletal muscle mitochondria to endurance training in HD patients.Thirteen HD patients and 11 healthy controls completed 26 weeks of endurance training. Before and after the training phase muscle biopsies were obtained from M. vastus lateralis. Mitochondrial respiratory chain complex activities, mitochondrial respiratory capacity, capillarization, and muscle fiber type distribution were determined from muscle samples.Citrate synthase activity increased during the training intervention in the whole cohort (P?=?0.006). There was no group x time interaction for citrate synthase activity during the training intervention (P?=?0.522). Complex III (P?=?0.008), Complex V (P?=?0.043), and succinate cytochrome c reductase (P?=?0.008) activities increased in HD patients and controls by endurance training. An increase in mass-specific mitochondrial respiratory capacity was present in HD patients during the endurance training intervention. Overall capillary-to-fiber ratio increased in HD patients by 8.4% and in healthy controls by 6.4% during the endurance training intervention.Skeletal muscle mitochondria of HD patients are equally responsive to an endurance-training stimulus as in healthy controls. Endurance training is a safe and feasible option to enhance indices of energy metabolism in skeletal muscle of HD patients and may represent a potential therapeutic approach to delay the onset and/or progression of muscular dysfunction.ClinicalTrials.gov NCT01879267 . Registered May 24, 2012.

SUBMITTER: Mueller SM

PROVIDER: S-EPMC5735536 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Effects of endurance training on skeletal muscle mitochondrial function in Huntington disease patients.

Mueller Sandro Manuel SM Gehrig Saskia Maria SM Petersen Jens A JA Frese Sebastian S Mihaylova Violeta V Ligon-Auer Maria M Khmara Natalia N Nuoffer Jean-Marc JM Schaller André A Lundby Carsten C Toigo Marco M Jung Hans H HH

Orphanet journal of rare diseases 20171219 1

<h4>Background</h4>Mitochondrial dysfunction may represent a pathogenic factor in Huntington disease (HD). Physical exercise leads to enhanced mitochondrial function in healthy participants. However, data on effects of physical exercise on HD skeletal muscle remains scarce. We aimed at investigating adaptations of the skeletal muscle mitochondria to endurance training in HD patients.<h4>Methods</h4>Thirteen HD patients and 11 healthy controls completed 26 weeks of endurance training. Before and ...[more]

PMID: 29258585

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Project description:The molecular pathways which are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ~800 gene transcripts are regulated following 6 weeks of supervised endurance training in young sedentary males, referred to as the training responsive transcriptome (TRT). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as over-represented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9 and PAX3 were down-regulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, pro-angiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA level validation there were several DNA variants that associated with VO(2)max trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption. This data is from skeletal muscle post 6 weeks of endurance exercise training.

Dataset Information

Effects of endurance training on skeletal muscle mitochondrial function in Huntington disease patients.

Publications

Effects of endurance training on skeletal muscle mitochondrial function in Huntington disease patients.

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