Sprint interval exercise drives a unique transcriptional mitochondrial stress response in humans
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE302582 | GEO | 2025/11/06
REPOSITORIES: GEO
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Project description:The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g. high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in 5 male sport team members using a repeated measures design of: 1) Change of direction (COD) versus; 2) straight line (ST) exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 minutes and 24 hours post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed x distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 mins and 24 hrs post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 minutes post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We confirmed increased gene expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes, PPARGC1A (that encodes PGC1-α) and NR4A3 in COD vs. ST exercise. Overall, we demonstrate that increased physiological/metabolic load via change of direction exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise.
2021-01-21 | GSE162288 | GEO
Project description:Aim: To examine the global gene expression response to the profound metabolic and hormonal stress induced by acute sprint exercise. Methods: Healthy women and men (n=14) performed 3 all-out cycle sprints interspersed by 20 min recovery. Muscle biopsies were obtained before the first and 2h and 20 min after the last sprint. Microarray analysis was performed to analyse the acute gene expression response. Repeated blood sample were also obtained. Results: In skeletal muscle, a set of immediate early genes, FOS, NR4A3, MAFF, EGR1, JUNB were markedly upregulated after sprint exercise. These genes were also upregulated, but to a lesser extent, after other exercise modes and after insulin exposure. Gene ontology analysis from 879 differentially expressed genes revealed predicted activation of extracellular remodelling and fat metabolism, which was in common with the gene expression response to endurance and resistance exercise. Moreover, the gene expression pattern indicated an increased turnover of skeletal muscle mass after sprint exercise, which was in common with data on resistance exercise and GH exposure. Insulin and GH may be involved in sprint-induced changes in the transcriptome, based on the overlap noted between sprint- and hormone exposure-related signatures. Furthermore, there were correlations between sprint-induced changes in hormonal levels and changes in gene expression. Conclusion: This is the first study reporting on global gene expression in skeletal muscle in response to acute sprint exercise. Several novel findings are presented related to novel sprint exercise - regulated genes as well as to shared gene signatures between sprint exercise, other exercise modes and exogenous hormone exposure.
2019-02-09 | GSE126296 | GEO
Project description:Skeletal muscle tissue is a highly adaptable tissue, responding to the specific demands it is subjected to. High-intensity interval training (HIIT) has been shown to generate similar, or even greater, molecular changes in skeletal muscle as that of constant load longer-lasting endurance-type training at moderate intensities. Despite shorter exposure times, the higher intensity provided by HIIT training leads to greater metabolic perturbations and thereby larger improvements in mitochondrial content and maximal oxygen uptake. During a period of regular exercise training, the performance improvements follow a non-linear pattern with a relatively faster pace initially and a gradual ‘plateauing-off’ after weeks and months. It is believed that this ‘plateau effect’ is due to a blunting of the molecular responses to acute exercise with exercise training. In the present study we utilised an explorative global transcriptomic approach to investigate the phenomenon of transcriptional-level blunting of the acute exercise response in human skeletal muscle over the course of a three-week HIIT intervention. We hypothesize that the blunting of transcription at this time-point is specific to certain pathways, including metabolic regulation and that these genes have communal transcriptional regulation.
2021-09-01 | GSE163356 | GEO
Project description:Exercise is an effective strategy in the prevention and treatment of metabolic diseases. Alterations in the skeletal muscle proteome, including post-translational modifications, regulate its metabolic adaptations to exercise. Here, we examined the effect of high-intensity interval training (HIIT) on the proteome and acetylome of human skeletal muscle, revealing the response of 3168 proteins and 1263 lysine acetyl-sites on 464 acetylated proteins. We identified novel protein adaptations to exercise training involved in metabolism and excitation-contraction coupling. Furthermore, HIIT increased the acetylation of mitochondrial proteins, particularly those of complex V, likely via non-enzymatic mechanisms. We also highlight the regulation of novel exercise-responsive histone acetyl-sites. These data demonstrate the plasticity of the skeletal muscle proteome and acetylome, providing insight into the regulation of contractile, metabolic and transcriptional processes within skeletal muscle. Herein, we provide a substantial hypothesis-generating resource to stimulate further mechanistic research investigating how exercise improves metabolic health.
2022-06-09 | PXD023084 | Pride
Project description:The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteins in concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages.
2017-03-28 | GSE97084 | GEO
Project description:Advances in mass-spectrometry (MS)-based technologies have leveraged our understanding of protein-wide adaptations in human skeletal muscle in response to exercise. However, there is a lack of such data in females, particularly pertaining to already trained females and menstrual cycle phase-based sprint interval training (SIT) despite its efficacy and popularity. Here, we present a comprehensive global proteome analysis of skeletal muscle adaptations to high-frequency SIT during different menstrual cycle phases in endurance-trained females. We randomized 49 eumenorrheic females to either high-frequency SIT in the follicular (FB) or luteal phase (LB) over one menstrual cycle comprising eight sessions of 6×30-s all-out efforts. MS-proteomics, covering 4155 proteins after filtering, revealed notable differences in muscle adaptations to phase-based SIT. LB suppressed mitochondrial pathways of the tricarboxylic acid cycle and electron transport chain while enriching ribosomal complexes. Conversely, FB enriched filament organization and skeletal system development. Mitochondrial repression during LB was linked to reduced O2max, whereas exercise capacity improved in FB only. Our findings show that menstrual cycle phase-based high-frequency SIT induces distinct protein-wide muscle adaptations and affects phenotype in endurance-trained eumenorrheic females.
2025-08-21 | PXD051852 | Pride
Project description:Genome wide DNA methylation profiling of post-exercise milk product intake during interval walking training. The Illumina Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in peripheral blood samples. Samples include 24 subjects (12, placebo intake; 12, milk product intake).
2017-06-09 | GSE76503 | GEO
Project description:The aim is to investigate the impact of prostate and colorectal cancer on mitochondrial quantity and quality along with muscle mass and function and whether this can be modified through the use of a home-based short-term exercise training program.
The investigators aim to recruit participants awaiting curative surgery for colorectal and prostate cancer and to assess the variation in baseline mitochondrial activity between them.
Participants from both cancer types will then carry out a 4 week home exercise program, this will be randomly allocated to either resistance-based or high-intensity interval training based. Participants will then be re-assessed on the day of their planned surgical procedure to assess the changes effected by the training program.
The investigators hypothesize that there will be variation in mitochondrial activity linked to muscle mass across the two cancer types and that home-based exercise programs have the ability to improve mitochondrial activity along with muscle mass.
| 2352291 | ecrin-mdr-crc
Project description:Exercise has been shown to improve health status and prevent the progression and development of numerous chronic diseases associated with chronic inflammation
2018-11-12 | MSV000083129 | MassIVE
Project description:The primary aim of this study was to compare the acute effects of three exercise intensities on abdominal subcutaneous adipose tissue (aSAT) transcriptome in regular exercisers. A total of 45 adults who exercise regularly were assigned to perform a single session of either low-intensity continuous (LOW; 60min at 30% VO2max; n=15), moderate-intensity continuous (MOD; 45min at 65% VO2max; n=15), or high-intensity interval exercise (HIGH; 10x1min at 90% VO2max interspersed with 1min active recovery; n=15). aSAT biopsy samples were collected before and 1.5hours after the exercise session for bulk RNA sequencing and targeted protein immunoassays. HIGH upregulated genes involved in cytokine secretion, insulin signaling, and proteolysis while MOD and LOW upregulated genes regulating ECM remodeling, ribosome biogenesis, and oxidative phosphorylation pathways. Exercise-induced changes in aSAT angiogenic, MAPK cascade, and clock genes, ERK protein phosphorylation, and circulating cytokines were similar after all three exercise treatments. Network analysis identified exercise-responsive gene clusters linked to cardiometabolic health traits. Cell-type analysis highlighted a heterogeneous response of aSAT cell types to exercise, with distinct patterns observed across exercise intensities. Collectively, our data characterizes early responses in aSAT after a single session of exercise. Because adaptations to exercise training stem from an accrual of responses after each session of exercise, these early responses to exercise are likely important contributors to the long-term structural and functional changes that occur in adipose tissue in response to exercise training.
2025-10-21 | GSE303983 | GEO