Three types of exercise affect specific muscle proteins

Health and Wellness 27. sep 2022 3 min Professor Erik A. Richter Written by Kristian Sjøgren

Researchers have identified 420 proteins in skeletal muscle that are all affected by endurance, sprint and resistance exercise. Eighty of these proteins also appear to be relevant to disease, and the researchers also identified a previously unknown function of one of these proteins.

Some people are into long runs, others lift heavy weights in the gym, and then some prefer explosive exercise such as sprinting.

These different types of exercise change the body in different ways, with resistance exercise leading to muscle growth and endurance exercise improving endurance. The body adapts when various molecular signals are transmitted when the muscles work.

New research shows that 5,486 proteins in the muscles are affected by one or more of three types of exercise – endurance, sprint and resistance – and that 420 of these are affected by all three types. These proteins therefore probably play a role in the health-promoting effects of physical activity.

“We have identified the core signalling that is activated during all types of exercise. If you delve deeper into the various proteins, you can more specifically see which signalling pathways are affected by acute activity and how this affects the body,” explains a researcher involved in this international study, Erik A. Richter, Professor, August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sport, University of Copenhagen.

The research has been published in Cell Metabolism.

Young men carried out various types of exercise

The researchers investigated how different types of exercise affect the phosphorylation of proteins in the muscles. Phosphorylation adds phosphate groups to proteins, changing their function. Some become more active and others less active.

Eight healthy men were asked to carry out different types of exercise on three different days:

  • endurance exercise for 90 minutes on a bicycle ergometer;
  • resistance exercise with the legs for 15 minutes; and
  • three times 30 seconds of sprinting on a bicycle ergometer.

The researchers then biopsied the participants’ thigh muscles before and immediately after the exercise and again after 3 hours of recovery. They sent the samples for mass spectrometry analysis to colleagues in Melbourne, Australia. Researchers can use mass spectrometry to determine the content of proteins in a biological sample and whether the proteins are phosphorylated or not.

“We know that phosphorylation is one of the most important ways in which the body can change the function of a protein. Phosphorylation can therefore be used to measure the extent to which exercise changes the function of specific proteins,” says Erik A. Richter.

420 proteins affected by all three types of exercise

The results showed that at least one of the three types of exercise changed the phosphorylation of 5,486 proteins in the muscles, and all three types changed the phosphorylation of 420 of these proteins.

Erik A. Richter calls these 420 proteins core proteins, because they are always activated, regardless of the type of exercise.

“We therefore also assume that some of these proteins are involved in the universally beneficial effects of physical activity,” he explains.

80 of the 420 proteins are relevant for disease

In the second part of the study, the researchers linked the 420 proteins to large databases of genes involved in various diseases such as type 2 diabetes. Eighty of the 420 proteins were in the databases and probably affect the development of disease.

Of the 80 proteins, the researchers selected for further study C18ORF25, which was linked to the risk of developing type 2 diabetes in the genome-wide association studies databases. This means that mutations in C18ORF25 increase the risk of developing type 2 diabetes.

The researchers then created knockout mice that genetically lack the ability to make C18ORF25 and examined how this affected them.

“The mice did not actually have problems with glucose metabolism, but their muscles performed less well at contracting and were smaller than in mice with a functional gene for C18ORF25. Further, the calcium metabolism of the muscles was impaired when the mice could not produce the protein,” says Erik A. Richter.

The researchers also reintroduced the protein into the mice that could not produce it themselves, and this restored normal muscle function.

Erik A. Richter explains that the study is basic science but may form the basis for further research that can produce knowledge on the universal positive effects of exercise.

“Now that we have identified the core phosphorylations, we have narrowed down the various possibilities for finding new health-promoting targets. We still have a major task in characterising the other 79 proteins, but at least we have shown how it can be done, thus identifying an important function of a previously uncharacterised protein relevant to the beneficial effects of exercise,” he says.

The Danish scientists behind the study are Erik A. Richter, Bente Kiens, Thomas E. Jensen, Christian Strini Carl and Christian T. Voldstedlund, all from the August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sport, University of Copenhagen. The Melbourne group was led by Benjamin L. Parker at the University of Melbourne.

Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as an AMPK substrate regulating skeletal muscle function” has been published in Cell Metabolism. The Novo Nordisk Foundation awarded a grant to Erik A. Richter in 2017 for the project Defining the AMPK-mediated Signalling Network and its Function and a grant in 2018 for the project Discovery and Validation of Muscle Signalling Related to Health.

My primary research interests are regulation of muscle metabolism, particularly during and following exercise. This includes acute exercise and exerci...

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