Exercise regularly is one of the best protections against metabolic diseases, such as obesity and diabetes – but why? It is a question that scientists are still struggling to answer. While exercise alters muscle molecular behavior, it is not understood how these molecular changes improve metabolic health.
Scientists at the University of Copenhagen have now developed a new technology that will allow researchers to study muscle biology at a more detailed level – and hopefully find some new answers. They extracted ‘fast’ and ‘slow’ muscle fibers from frozen dried muscle samples taken before and after 12 weeks of cycling exercise training. Their complete analysis of the protein expression of the fibers provides new evidence that the fiber types respond differently to exercise training.
The research, published in Nature Communications, also shows the undeveloped potential of freeze-dried samples located in freezers around the world.
Metabolic disorders and several muscle diseases are known to affect or destroy certain fiber types, so a detailed study of specific fiber types is essential. Previous studies included large-scale protein analysis of skeletal muscle requiring isolation of single muscle masses from newly obtained muscle biopsies. Because muscle fiber isolation takes a long time, this approach has sexual limitations. Our method enables muscle fiber analysis of already collected muscle biopsies as well as being a new method for future studies. “
Atul Deshmukh, Professional Professor, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), University of Copenhagen
False and confused muscle samples
A skeletal muscle contains tiny fibers that can be classified as either fast or slow. Simply put, fast twitch threads generate explosive energy but quickly become tired, while slow twitch threads are less energetic but have more durability. Their muscles have an equal number of both types, but the ratio can vary widely between people. This means that exercise may benefit people in a different way, depending on this ratio.
In a muscle, thousands of needles are tied together with a connective tissue and surrounded by a range of cell types with supporting function. Because of these different cell types, scientists may struggle to interpret whole muscle sample results, and link observed changes in specific cell types.
Realizing the potential of individual fiber studies, Atul Deshmukh was joined by Professor Matthias Mann from the Novo Nordisk Foundation Center for Protein Research, and the Wojtaszewski Group from the Department of Nutrition, Exercise and Sport, both at the University of Copenhagen.
Ingestion of muscle fiber
They recruited healthy people for 12 weeks of endurance exercise training and collected muscle samples before and after exercise, which were then freely dehydrated. They then extracted fast and slow-twitch muscle fibers from the samples and performed high-mass proteomics based on spectrometry – a device that allows scientists to quantify thousands of proteins simultaneously in the various samples.
They identified more than 4,000 different proteins in the samples, and found that exercise training altered the sensation of hundreds of different proteins in both fast and slow-twitch fiber types. Importantly, they found differences in the protein expression of the two types of fiber after exercise, which show that fast and slow leg muscles respond differently.
“Our approach can be scaled for high-throughput analysis of hundreds of individual muscle fibers from a single biopsy. Combining this approach with the modern high-sensitivity mass spectrometer could help understanding fiber-type heterogeneity in healthy and diseased skeletal muscle, ”says Associate Professor Atul Deshmukh of the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.
Drugs that do not target the heart unknowingly
With mass, skeletal muscle is the largest organ in the body and even small changes can have a major impact on the body’s overall metabolism. Skeletal muscle is therefore an interesting pharmacological target substance with great potential in the treatment of metabolic diseases. One challenge is to avoid side effects in a heart muscle, for example, which is made up of a certain wood with some things that seem to slow down skeletal muscle.
“So our unique fiber-type protein deposition is the first step toward identifying skeletal muscle proteins that are specific for fast twitch fiber, allowing drug targeting and delivery to this specific fiber type and which may avoid side effects in the heart, “says Dr. Jørgen Wojtaszewski from the Department of Nutrition, Exercise and Sport at the University of Copenhagen.
Source:
University of Copenhagen – Faculty of Health and Medical Sciences
Magazine Reference:
Deshmukh, AS, et al. (2021) In-depth muscle-proteomic analysis of dried human muscle biopsies reveals specific changes specific to fiber for exercise training. Nature Communication. doi.org/10.1038/s41467-020-20556-8.