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

ABSTRACT: 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 global protein adaptations to exercise training involved in metabolism, excitation-contraction coupling, and myofibrillar calcium sensitivity. Furthermore, HIIT increased the acetylation of mitochondrial proteins, particularly those of complex V. We also highlight the regulation of 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.

SUBMITTER: Hostrup M

PROVIDER: S-EPMC9154743 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Hostrup Morten M Lemminger Anders Krogh AK Stocks Ben B Gonzalez-Franquesa Alba A Larsen Jeppe Kjærgaard JK Quesada Julia Prats JP Thomassen Martin M Weinert Brian Tate BT Bangsbo Jens J Deshmukh Atul Shahaji AS

eLife 20220531

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 global protein adaptations to exerc ...[more]

PMID: 35638262

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Project description:Ten healthy male participants were recruited and successfully completed all preliminary testing and the two exercise bouts (Figure 1A). This randomized crossover design permitted signaling responses to workload- and duration-matched HIIT and MICT exercise to be mapped and interrogated within the same participant. Baseline whole-body anthropometric and blood glucose and lipid measurements confirmed these participants (age 25.4 ± 3.2 y; BMI 23.5 ± 1.6 kg/m2) were metabolically healthy, and maximal exercise capacity testing confirmed they were recreationally active but relatively untrained (relative V̇O2 peak 37.9 ± 5.2) in line with our recruitment strategy to maximize detection of skeletal muscle signaling responses to exercise (Figure 1B). Peak power output (Wpeak; 207.5 ± 40.3 W) was used to prescribe the relative work-matched intensities for HIIT and MICT. Lean mass from the DXA scan and resting metabolic rate (Figure 1B) were used to prescribe a standardized meal for each participant to consume prior to each exercise trial day. Following consumption of a standardized dinner meal the night before the HIIT or MICT exercise trial, blood and skeletal muscle biopsy samples were collected in the fasted state at baseline and at 5 min and 10 min of each respective exercise intensity. Participants completing the acute bout of HIIT, which consisted of 10 min total of 1-min ‘on’ intervals at 85 ± 0.1% of individual Wpeak (176 ± 34 W) and 1-min ‘off’ intervals at 50 W, displayed increased plasma lactate concentrations at 5 and 10 min of exercise relative to pre-exercise baseline (Figure 1C; P < 0.0001 and P < 0.001, respectively; main effect of time P < 0.0001) and no changes in plasma glucose (Figure 1D). In response to total work- and duration-matched acute bout of MICT at 55 ± 2% individual Wpeak (113 ± 17 W), participants displayed increased plasma lactate concentrations at 5 and 10 min of exercise versus baseline (Figure 1C; P < 0.001; main effect of time P < 0.0001) and no changes in plasma glucose (Figure 1D), with a main effect of higher plasma lactate levels in response to HIIT (Figure 1C; P < 0.05). To map the signaling networks regulated by HIIT and MICT, proteins from each skeletal muscle biopsy sample were extracted, digested to peptides with trypsin, isobarically labelled prior to phosphopeptide enrichment, fractionation and LC-MS/MS phosphoproteomic analysis (Figure 2A).

Dataset Information

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

Publications

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

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