High-intensity interval training remodels the proteome and acetylome of human skeletal muscle
Curation statements for this article:-
Curated by eLife
Evaluation Summary
This paper will be of interest to readers in the fields of exercise physiology, muscle biology and energy metabolism. The authors provide a proteomic resource where changes in the skeletal muscle proteome and acetyl-proteome have been assessed following the increasingly popular exercise intervention of high intensity interval training (HIIT). The adaptive responses reported provide new insight into the metabolic, contractile and transcriptional changes in muscle, and may represent an excellent resource for stimulating future focussed molecular studies in the field.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (eLife)
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.
Article activity feed
-
-
-
-
-
-
-
Evaluation Summary
This paper will be of interest to readers in the fields of exercise physiology, muscle biology and energy metabolism. The authors provide a proteomic resource where changes in the skeletal muscle proteome and acetyl-proteome have been assessed following the increasingly popular exercise intervention of high intensity interval training (HIIT). The adaptive responses reported provide new insight into the metabolic, contractile and transcriptional changes in muscle, and may represent an excellent resource for stimulating future focussed molecular studies in the field.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)
-
Reviewer #1 (Public Review):
The authors examined the effect of high-intensity interval training (HIIT) on the proteome and acetylome of human skeletal muscle. HIIT altered the abundance of proteins involved in metabolism, excitation-contraction coupling and myofibrillar calcium sensitivity. In addition, HIIT increased the acetylation of mitochondrial proteins, particularly those of complex V. They further investigated the mechanism of acetylation. In addition, they found changes of some histone acetylation before and after HIIT.
One of the strengths of this manuscript is that the authors obtained the comprehensive proteome and acetylome from human skeletal muscles before and after HIIT, which are publicly available and considered to be important resources. The procedures for sample acquisition, measurements, and analyses are clearly …
Reviewer #1 (Public Review):
The authors examined the effect of high-intensity interval training (HIIT) on the proteome and acetylome of human skeletal muscle. HIIT altered the abundance of proteins involved in metabolism, excitation-contraction coupling and myofibrillar calcium sensitivity. In addition, HIIT increased the acetylation of mitochondrial proteins, particularly those of complex V. They further investigated the mechanism of acetylation. In addition, they found changes of some histone acetylation before and after HIIT.
One of the strengths of this manuscript is that the authors obtained the comprehensive proteome and acetylome from human skeletal muscles before and after HIIT, which are publicly available and considered to be important resources. The procedures for sample acquisition, measurements, and analyses are clearly described. Although there have been previous studies analyzing acetylome in skeletal muscle (Lundby et al., 2012), they newly found the selective acetylation of mitochondrial complex V after HIIT. A weakness of the manuscript is that there is little evidence to support the non-enzymatic acetylation.
-
Reviewer #2 (Public Review):
In this study, Hostrup et al., set out to determine how 5 weeks of HIIT training alters the proteome and acetylome in skeletal muscle. Some of the major findings from the proteomic data include evidence for HIIT-induced mitochondrial biogenesis and potentially a HIIT-induced "slowing" of the muscle properties, whereas the major findings from the acetylome data include evidence of HIIT-induced acetylation of mitochondrial proteins as well as HIIT-induced acetylation of proteins that are involved in the TCA cycle.
-
Reviewer #3 (Public Review):
This study by Hostrup et al. examines the remodelling of the proteome and acetyl-proteome in skeletal muscle following a period of high intensity interval training (HIIT). The subjects were exposed to a 5 week HIIT protocol, which produced the desired training effect, as demonstrated by physiological and biochemical changes observed at the level of the whole-body and skeletal muscle respectively. Assessment of the proteome revealed a number of 'predictable' training-induced changes, such as increased abundance of several mitochondrial proteins. Additionally, changes were observed in a number of other novel proteins and pathways, highlighting adaptive changes that facilitate the broader physiological effects and benefits of exercise training. The acetyl-proteomics revealed altered acetylation status in a …
Reviewer #3 (Public Review):
This study by Hostrup et al. examines the remodelling of the proteome and acetyl-proteome in skeletal muscle following a period of high intensity interval training (HIIT). The subjects were exposed to a 5 week HIIT protocol, which produced the desired training effect, as demonstrated by physiological and biochemical changes observed at the level of the whole-body and skeletal muscle respectively. Assessment of the proteome revealed a number of 'predictable' training-induced changes, such as increased abundance of several mitochondrial proteins. Additionally, changes were observed in a number of other novel proteins and pathways, highlighting adaptive changes that facilitate the broader physiological effects and benefits of exercise training. The acetyl-proteomics revealed altered acetylation status in a range of different pathways (likely via non-enzymatic mechanisms), with prominent alterations to respiratory Complex V, TCA cycle enzymes and histone proteins.
While observational in nature, the study was performed in a robust manner, the conclusions are largely supported by the data, and the outputs collectively provide a rich resource for future hypothesis-driven examinations of mediators of the skeletal muscle response to exercise training. There are a few points noted below that would benefit from extended discussion and potentially a few additional experiments.
-
-