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Genome-wide DNA methylation and mRNA responses to a bout of higher versus lower load resistance training in previously trained men

ABSTRACT: Genome-wide DNA methylation and mRNA responses to a bout of higher versus lower load resistance training in previously trained men

PROVIDER: PRJNA911819 | ENA |

REPOSITORIES: ENA

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Project description:We sought to determine skeletal muscle genome-wide DNA methylation and transcriptome changes to one bout of lower-load (LL) versus higher-load (HL) resistance exercise. Previously trained college-aged males (n=11, age: 23±4 years old, training experience: 4 ± 3 years) performed LL or HL bouts to failure separated by one week. The HL bout (a.k.a., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of their estimated one-repetition maximum (i.e., est. 1-RM from 3-RM testing), whereas the LL bout (a.k.a., 30 Fail) consisted of this same paradigm using 30% of their est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 hours, and 6 hours after each exercise bout. DNA and RNA were batch-isolated from muscle and analyzed for genome-wide DNA methylation and mRNA expression using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Although the total number of repetitions performed were significantly greater during the 30 Fail versus 80 Fail bout (p<0.001), total training volume (sets x reps x load) was not significantly different between conditions (p=0.571). Interestingly, 30 Fail led to decreased methylation across various promoter regions, albeit the transcriptome-wide responses between bouts were largely similar. According to bioinformatics, both bouts altered post-exercise mRNA profiles related to inflammatory signaling (e.g., Toll receptor, CCKR, chemokine and cytokine signaling), apoptosis, gonadotropin-releasing hormone, and integrin signaling. Also notable, more robust DNA methylation events occurred 3 hours versus 6 hours post-exercise regardless of bout (239,951 versus 12,419 CpG sites significantly hyper- or hypomethylated at these respective time points, p<0.01). Moreover, the percentage of significantly altered mRNAs that also demonstrated significantly inversed methylation patterns across one or more CpG sites was appreciably higher at 3 hours versus 6 hours following exercise (~75% versus ~15%, respectively). In conclusion, our transcriptomic data suggest that the molecular signaling events during the early post-exercise period are largely similar between LL and HL bouts, and this may explain why similar longer-term phenotypes (e.g., myofiber hypertrophy) result from these two training modalities. Additionally, our methylome data indicate that the majority of DNA methylation changes following an acute bout of resistance exercise occur rapidly (~3 hours) following exercise in previously trained men.

Project description:We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA respons-es to one bout of lower-load (LL) versus higher-load (HL) resistance exercise. Trained col-lege-aged males (n=11, 23±4 years old, 4±3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 hours, and 6 hours after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina Methyl-ationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were sig-nificantly greater during the 30 Fail versus 80 Fail (p<0.001), although total training volume (sets x reps x load) was not significantly different between bouts (p=0.571). Regardless of bout, more CpG site methylation changes were observed at 3- versus 6-hours post exercise (239,951 versus 12,419, respectively; p<0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3- and 6-hours following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3- versus 6-hours following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 hours fol-lowing exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 hours following exercise (65% and 82%, respectively). While 30 Fail de-creased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar be-tween bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to “Focal adhesion”, “MAPK signaling”, and “PI3K-Akt signaling” were sig-nificantly affected at the 3- and 6-hour time points, and again this was regardless of bout. In con-clusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts.

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Genome-wide DNA methylation and mRNA responses to a bout of higher versus lower load resistance training in previously trained men

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