High-intensity interval training remodels the proteome and acetylome of human skeletal muscle

Hostrup, Morten; Lemminger, Anders Krogh; Stocks, Ben; González-Franquesa, Alba; Larsen, Jeppe K.; Quesada, Júlia Prats; Thomassen, Martin; Weinert, Brian T.; Bangsbo, Jens; Deshmukh, Atul S.

doi:10.7554/elife.69802

Cited by 34 publications

(43 citation statements)

References 103 publications

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“…6D, S10E). Interestingly, increased acetylation of Complex V with exercise training has also been observed in human skeletal muscle 53 , supporting the relevance of our findings for human mitochondrial adaptation. Acetylation of mitochondrial proteins is an important mechanism for regulating fatty acid metabolism 54 , as well as Complex I activity 55 , although the effect of site-specific changes on enzymatic activity remains largely unknown.…”

Section: Resultssupporting

confidence: 88%

“…However, exercise is known to protect hepatic metabolic health and improve oxidative capacity and our results also show dramatic increases in acetylation in response to training. Moreover, exercise training also increases protein acetylation in skeletal muscle 53,82 , which is attributed to improvements in mitochondrial function following training. We observed increased acetylation of mitochondrial proteins in both liver and heart despite a concomitant increase in SIRT3, a mitochondria-specific deacetylase.…”

Section: Discussionmentioning

confidence: 99%

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The mitochondrial multi-omic response to exercise training across tissues

Amar

Gay

Jimenez-Morales

et al. 2023

Preprint

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Mitochondria are adaptable organelles with diverse cellular functions critical to whole-body metabolic homeostasis. While chronic endurance exercise training is known to alter mitochondrial activity, these adaptations have not yet been systematically characterized. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) mapped the longitudinal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats endurance trained for 1, 2, 4 or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart and skeletal muscle, while we detected mild responses in the brain, lung, small intestine and testes. The colon response was characterized by non-linear dynamics that resulted in upregulation of mitochondrial function that was more prominent in females. Brown adipose and adrenal tissues were characterized by substantial downregulation of mitochondrial pathways. Training induced a previously unrecognized robust upregulation of mitochondrial protein abundance and acetylation in the liver, and a concomitant shift in lipid metabolism. The striated muscles demonstrated a highly coordinated response to increase oxidative capacity, with the majority of changes occurring in protein abundance and post-translational modifications. We identified exercise upregulated networks that are downregulated in human type 2 diabetes and liver cirrhosis. In both cases HSD17B10, a central dehydrogenase in multiple metabolic pathways and mitochondrial tRNA maturation, was the main hub. In summary, we provide a multi-omic, cross-tissue atlas of the mitochondrial response to training and identify candidates for prevention of disease-associated mitochondrial dysfunction.

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Section: Resultssupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

The mitochondrial multi-omic response to exercise training across tissues

Amar

Gay

Jimenez-Morales

et al. 2023

Preprint

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“…A recent paper investigating the effects of training in the human proteome and acetylome identified novel exercise-training regulated proteins including glutaminyl-tRNA synthase (QARS) and rab GDP dissociation inhibitor alpha (GDI1) [87]. These proteins are associated with insulin-stimulated glucose uptake and may provide a novel mechanism explaining the role of exercise training in insulin-sensitizing effects.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation and proteomics integration uncover dose-dependent group and individual responses to exercise in human skeletal muscle

Michaux

Landen

Alvarez-Romero

et al. 2022

Preprint

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Objective: Exercise is a major regulator of muscle metabolism, and health benefits acquired by exercise are a result of molecular shifts occurring across multiple OMIC levels (i.e. epigenome, transcriptome, proteome). Identifying robust targets associated with exercise response, at both group and individual levels, is therefore important to develop health guidelines and targeted health interventions. Methods: Twenty, apparently healthy, moderately trained (VO2 max= 51.0 sd= 10.6 mL/min/kg) males (age range= 18-45yrs) from the Gene SMART (Skeletal Muscle Adaptive Responses to Training) study completed a 12-week High-Intensity Interval Training (HIIT) intervention. Muscle biopsies were collected at baseline and after 4, 8, and 12 weeks of HIIT. High throughput DNA methylation (~850 CpG sites), and proteomic (~3000 proteins) analyses were conducted at all-time points. Mixed-models were applied to estimate group and individual changes, and methylome and proteome integration was conducted using a holistic multilevel approach with the mixOmics package. Results: Significant shifts in the methylome (residual analysis) and proteome profiles were observed after 12 weeks of HIIT. 461 proteins significantly changed over time (at 4, 8, and 12 weeks), whilst only one differentially methylated position (DMP) was changed (adj.p-value <0.05). K-means analysis revealed clear protein clustering exhibiting similar changes over time. Individual responses to training were observed in 101 proteins. Seven proteins had a large effect-sizes >0.5, among them are two novel exercise- related proteins, LYRM7 and EPN1. Integration analysis uncovered bidirectional relationships between the methylome and proteome. Conclusions: We showed a significant influence of HIIT on the epigenome and proteome in human muscle, and uncovered groups of proteins clustering according to similar patterns across the exercise intervention. Individual responses to exercise were observed in the proteome with novel mitochondrial and metabolic proteins consistently changed across individuals. Future work is required to elucidate the role of such proteins in response to exercise as well as to investigate the mechanisms associating genes and proteins in response to exercise.

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Section: Aerobic High-intensity Trainingmentioning

confidence: 99%

“…Aside from augmenting , a period of aerobic high-intensity training induces numerous beneficial adaptations, which include peripheral adaptations in the microvasculature and oxidative capacity of skeletal muscle [ 104 – 108 ]. While not extensively examined in elite football players, aerobic high-intensity training increases capillary density and expands mitochondrial volume in skeletal muscle fibers [ 104 – 108 ]. In semi-professional players returning from intermission, 4 weeks of high-intensity training enhanced the capacity for oxidative metabolism of the trained muscle as reflected by an increased capillary density and in vitro maximal activity of citrate synthase and hydroxyacyl-CoA dehydrogenase (HAD) in muscle homogenates [ 109 ].…”

Section: Aerobic High-intensity Trainingmentioning

confidence: 99%

Performance Adaptations to Intensified Training in Top-Level Football

Hostrup

Bangsbo

2022

Sports Med

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Because physical demands are surging in football (soccer, USA), clubs are more and more seeking players who have a high capacity to perform repeated intense exercise. High-intensity interval training (HIIT), comprising exercise performed at intensities near or exceeding the capacity of aerobic energy systems, effectively enhances the physical conditioning of players. But given that HIIT imposes high loads, it increases the risk of overload-associated match performance decline and injury. This makes some coaches inclined to conduct HIIT in the weeks leading up to the season and during the season. Therefore, the challenge is how to optimize and dose HIIT during these phases, as they can be decisive. Studies have highlighted the utility of conducting periods of intensified training to overcome the risk of overload while at the same time enhancing performance. During intensified training periods of typically a few weeks, intensity is increased by enlarging the amount of HIIT, for example, aerobic high-intensity training or speed endurance training, while volume at low-to-moderate intensity is significantly reduced. The outcome depends on training composition and prescription—most notably, intensity and duration of bouts and recovery. When work intervals are prescribed for a few minutes at intensities > 90% heart rate max (i.e., aerobic high-intensity training), then beneficial adaptations pertaining to aerobic power and capacity are apparent. But when work intervals are conducted at much higher intensities, as all-out efforts or sprinting of typically 10- to 40-s duration with longer recovery periods (i.e., speed endurance training), beneficial adaptations pertaining to anaerobic energy systems, ion handling, and fatigue resilience are commonly observed. In this review, we discuss the utility of conducting intensified training periods to enhance performance in elite football players during the late preparation phase and competitive season.

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High-intensity interval training remodels the proteome and acetylome of human skeletal muscle

Cited by 34 publications

References 103 publications

The mitochondrial multi-omic response to exercise training across tissues

The mitochondrial multi-omic response to exercise training across tissues

DNA methylation and proteomics integration uncover dose-dependent group and individual responses to exercise in human skeletal muscle

Performance Adaptations to Intensified Training in Top-Level Football

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