Different types of exercise have different effects on how muscle cells express proteins. New research shows how a few weeks of high-intensity interval training affects protein regulation and what this may mean for how adaptable the muscle cells are. A researcher involved in the study say that the discovery might also be useful in understanding the beneficial effects of exercise in various diseases, including type 2 diabetes and muscular dystrophy.
Exercising is healthy. Whether it is resistance exercise, running in the forest, cycling or getting it all over quickly with 20 minutes of high-intensity interval training, all types of exercise strongly influence the body.
Exercise uniquely alters the protein expression in the muscle cells at the molecular level.
For example, resistance exercise places specific demands on the muscle cells and causes them to produce more of some types of proteins and less of others. Endurance exercise yields completely different results, with the muscle cells instead producing more of a different set of proteins.
Exercise regulates several thousand proteins. In addition to influencing the expression of proteins, exercise also affects post-translational modifications: that is, how proteins are regulated after being expressed.
A new study shows how high-intensity interval training affects the expression of proteins in muscle cells and how this type of exercise likely makes the cells more adaptable to coping with various types of stress through post-translational modifications.
“It is fascinating to see how exercise regulates thousands of proteins in a network in the muscle cells. This makes us much more aware of the fundamental effects of exercise at the cellular level,” explains a researcher involved in the study, Morten Hostrup, Associate Professor, August Krogh Section for Human Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen.
The research, which has been published in eLife, was carried out by Morten Hostrup in collaboration with colleagues, including Atul Shahaji Deshmukh, Associate Professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.
Young men exercised intensely
The researchers asked eight untrained men aged 23–38 years to perform high-intensity interval training on an exercise bike for 5 weeks, with three sessions per week.
The researchers collected thigh muscle biopsies before and after the 5 weeks of training and used mass spectrometry–based proteomics to determine how the high-intensity interval training changed the composition of several thousand proteins in the muscle cells.
In addition, the researchers investigated post-translational modifications in the form of acetylation, in which an acetyl group is attached to the proteins or DNA.
“Acetylation is known to influence the functionality of proteins, the metabolism and how the DNA is mobilised to initiate the transcription of genes encoding proteins. We therefore wanted to understand how exercise affects protein acetylation,” says Morten Hostrup.
Exercise regulates thousands of proteins
The results show that high-intensity interval training strongly affects the expression of several hundred proteins in muscle cells and their acetylation.
Proteins involved in metabolic processes, muscle cell contraction and calcium sensitivity were especially remodelled after the 5 weeks of training.
Further, the expression of mitochondrial proteins changed substantially. The mitochondria are the cells’ power plants, and the more mitochondria the cells contain and the better they function, the more endurance the muscles have.
“Just 15 training sessions produced huge changes. This confirms how rapid and effectively exercise remodels proteins of importance for muscle cell functioning and metabolism and produces the accompanying health benefits,” explains Morten Hostrup.
In addition to changing the protein expression in the muscle cells, high-intensity interval training robustly enhanced the participants’ fitness and cardiometabolic health despite the short duration of the programme.
“We know that exercise is healthy and improves the function of the mitochondria, but until now we did not know much about the underlying mechanisms – let alone how exercise training regulates the acetylation of mitochondrial proteins. Our study indicates which proteins high-intensity interval training upregulates and downregulates, with the latter therefore being less essential. The same applies to acetylation. We can see how important acetylation is for the proteins to be adaptable to cope with the stress of regular interval training,” says Morten Hostrup.
Muscle cells become more adaptable
Morten Hostrup interprets the research as showing that the remodelling of protein expression and acetylation not only improves the endurance of the muscle cells but also makes them more adaptable.
The acetylation probably enables the cells to more rapidly mobilise the DNA and decode the genetic material when new proteins are needed to combat cellular stress.
This probably also enables the cells to recover more rapidly between exercise sessions because they can more easily replace worn-out proteins.
In fact, the results surprised the researchers, who had expected that exercise would make the muscle cells more able to cope with stress and therefore downregulate protein acetylation.
“But the opposite happened. Instead, the muscle cells seem more adaptable, so that they are ready to face the challenges presented to them in connection with exercise,” explains Morten Hostrup.
Different types of exercise affect muscles differently
The researchers investigated high-intensity interval training, but investigating the effects of resistance exercise or endurance running would have probably led to very different results, and completely different proteins would have been up- and downregulated. The same probably applies to acetylation.
Morten Hostrup explains that researchers are gradually understanding that different types of exercise have very different effects on the body. This applies not only to the physical changes in muscle size or the ability to run long distances but also at the molecular level and in the proteins.
“Once we determine how different types of exercise affect the proteins, acetylation and other post-translational modifications, we can start to compare them. This will advance knowledge about what happens in different types of exercise,” he says.
One relevant area to investigate is how different types of exercise affect proteins that are related to disease, such as the proteins that affect the development of type 2 diabetes or muscular dystrophy.
“We will obtain insight into which proteins are affected and which types of exercise are most beneficial for people with these diseases,” concludes Morten Hostrup.
