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Analysis of human subcutaneous adipose tissue from an 8-week training-intervention

ABSTRACT: The participants performed an 8-week supervised aerobic endurance exercise intervention program. Biopsies of both adipose tissue and skeletal muscle were collected at associated timepoints and a matched analysis was performed.

ORGANISM(S): Homo sapiens

PROVIDER: GSE208032 | GEO | 2023/02/01

REPOSITORIES: GEO

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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.

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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Analysis of human subcutaneous adipose tissue from an 8-week training-intervention

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