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Genetic and Epigenetic Regulation of Skeletal Muscle Ribosome Biogenesis with Exercise

ABSTRACT: Ribosomes are the macromolecular engines of protein synthesis. Factors mediating ribosome biogenesis in skeletal muscle that facilitate adaptation to exercise are multi-factorial, but may be related to ribosomal DNA (rDNA) dosage and/or epigenetic modifications to rDNA. To investigate these possibilities, we conducted reduced representation bisulfite sequencing (RRBS) on skeletal muscle biopsies from human subjects before and after exercise and to detect differences in methylation patterns during exercise adaptation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162392 | GEO | 2021/07/13

REPOSITORIES: GEO

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Project description: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).

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Genetic and Epigenetic Regulation of Skeletal Muscle Ribosome Biogenesis with Exercise

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