Unknown,Transcriptomics,Genomics,Proteomics

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Effects of a 8-week training on human skeletal muscle

ABSTRACT: Context: Exercise training is a plausible model for identification of molecular mechanisms that cause metabolic-related changes in human skeletal muscle. Objective: The goal was to explore the molecular basis of the adaptation of skeletal muscle to exercise training. Design and Intervention: Obese male subjects were subjected to an individualized supervised training program targeted in order to optimize lipid oxidation during 8 weeks. Main Outcome Measures: Primary outcome measures were gene expression profiling of skeletal muscle. Body composition, oral glucose tolerance test, Resting metabolic rate, respiratory quotient, maximal oxygen uptake and metabolic biochemistry were also assessed. Overall Design The obese (BMI 30-36) male volunteers (age 32-42) were asked to refrain from vigorous physical activity 48h before presenting to the clinical investigation centre, and ate a weight-maintaining diet consisting of 35% fat, 16% protein, and 49% carbohydrates two days before the experiment. Muscle biopsies of Vastus Lateralis weighing 60–100 mg were obtained using the Bergstrom technique, cleaned and snap-frozen in liquid nitrogen. Resting metabolic rate, respiratory quotient and maximal oxygen uptake were assessed. The subjects were investigated at baseline and after 8 weeks of supervised aerobic exercise training program consisting of daily sessions of 45-60 min of endurance exercise, 5 days a week, at least 48-72h after the last acute exercise bout. Skeletal muscle biopsies were obtained at the beginning and at the end of the protocol. Transcriptome analysis compared 8 subjects before vs. after training using arrays using a common reference design (Cy5 dye was incorporated into all muscle RNA samples, while a reference RNA pool made of the mix of commercial human liver, adipose tissue and skeletal muscle RNA was labelled with Cy3 dye (Applied Biosystems/Ambion, Foster City, USA)( and whole genome 4x44k oligonucleotide arrays (Agilent Technologies).

ORGANISM(S): Homo sapiens

SUBMITTER: Nathalie Viguerie

PROVIDER: E-GEOD-40551 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Natriuretic peptides enhance the oxidative capacity of human skeletal muscle.

Engeli Stefan S Birkenfeld Andreas L AL Badin Pierre-Marie PM Bourlier Virginie V Louche Katie K Viguerie Nathalie N Thalamas Claire C Montastier Emilie E Larrouy Dominique D Harant Isabelle I de Glisezinski Isabelle I Lieske Stefanie S Reinke Julia J Beckmann Bibiana B Langin Dominique D Jordan Jens J Moro Cedric C

The Journal of clinical investigation 20121101 12

Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPARγ coactivator-1α (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS ge ...[more]

PMID: 23114600

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Project description:We used gene microarray analysis to compare the global expression profile of genes involved in adaptation to exercise training in skeletal muscle from chronically strength/resistance trained (ST), endurance trained (ET) and untrained control subjects (Con). Resting skeletal muscle samples (~100mg) were obtained from the vastus lateralis of 20 subjects (Con n=7, ET n=7, ST n=6; trained groups >8 years specific training). Total RNA was extracted from tissue and microarrays completed, with test samples compared with standard human reference RNA. Subjects were characterised by performance measures of maximal oxygen uptake (VO2max) on a cycle ergometer and maximal concentric and eccentric leg strength on an isokinetic dynamometer. 263 genes were differentially expressed in trained (TR collectively ET + ST) subjects compared with Con (P<0.05) while 21 genes were different between ST and ET (P<0.05). Manual cluster analyses revealed significant regulation of genes involved in muscle structure and development in TR subjects compared with Con (P<0.05), and expression of these correlated significantly with measures of performance (P<0.05). ET had increased and ST decreased expression of gene clusters related to mitochondrial/oxidative capacity (P<0.05), and these mitochondrial gene clusters correlated significantly with VO2max (P<0.05). VO2max also correlated with expression of gene clusters that regulate fat and carbohydrate oxidation (P<0.05). We have demonstrated that chronic training has marked effects on basal gene expression by regulating levels of multiple mRNAs that transcribe genes for important functional groups in human skeletal muscle. Some specific gene clusters are expressed regardless of the training stimulus, whereas others exhibit divergent expression patterns as a result of specific training stimuli. Keywords: Comparative, cluster analysis, endurance training, strength training, muscle phenotype This was a crossectional study examining basal gene expression profiles of the human vastus lateralis. Twenty healthy males volunteered for this investigation. Seven were endurance trained cyclists (ET), who had been participating in endurance training for 8 yr. These subjects had no history of resistance training. Six subjects were strength trained power-lifters (ST) who had been participating exclusively in strength/resistance training for 9 yr. The final seven subjects were healthy controls (CON) that did not participate in any formal exercise. The study was approved by the Human Research Ethics Committee of RMIT University and Monash University Standing Committee on Ethics Research on Humans. After RNA extraction, amplification and indirect labelling, a dual colour micro-array analysis was conducted by hybridizing a test (muscle RNA; Cy5) sample and a reference (Universal human RNA; Cy3) sample on the AGRF glass slide human 8K micro-array. After data capture with the Genepix scanner and associated software data was normalised and the three populations compared using GeneSpring and simplified cluster analysis.

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 a 8-week training on human skeletal muscle

Publications

Natriuretic peptides enhance the oxidative capacity of human skeletal muscle.

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