Fundamental biochemistry of acute exercise mapped

Breaking new ground 1. feb 2021 3 min Associate Professor Christoffer Clemmensen Written by Kristian Sjøgren

The biochemical processes the body activates during exercise remain incompletely understood. However, new technology has enabled Danish researchers for the first time to map the fundamental molecular mechanisms behind acute bouts of endurance and resistance exercise.

Technological advances in recent years have revolutionized the understanding of how the human body works.

Genomics, proteomics and metabolomics have advanced researchers’ knowledge on genetics, proteins and the comprehensive analysis of the metabolome (the complete set of metabolites in a biological cell, tissue, organ or organism).

These new disciplines and technologies have enabled Danish researchers to map how acute endurance exercise and resistance exercise affect the metabolome, which represents what happens inside the body.

This mapping has the potential to lay the foundations of future insight into why exercise benefits health.

“Metabolomics enables us to examine fluctuations of many hundreds of metabolites in the blood to determine how different types of exercise uniquely affect human biology. This technology is relatively new and gives us an opportunity to advance our understanding of how the various types of exercise training benefit health,” explains Christoffer Clemmensen from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.

The research has been published in Cell Reports.

Exercise changes the levels of metabolites in the body

When you exercise, myriad biochemical processes in your body are responsible for making your arms and legs move as they should. This applies to endurance exercise, such as cycling, and resistance exercise, such as pumping iron at a local fitness centre.

The biochemical processes change the levels of countless compounds in the bloodstream, including metabolites: small molecules within cells, biofluid, tissues or organisms involved in the body’s overall metabolism.

An example is lactate, the concentrations of which increase in the blood during both resistance exercise and endurance exercise.

“Lactate is a well-known metabolite in the blood, but the unknown metabolites are just as interesting. Characterizing these metabolites in depth can provide more information on the still unknown benefits of exercise and how these are manifested in the body,” says Christoffer Clemmensen.

Mapping the metabolome of healthy men after acute exercise training

The researchers enrolled 10 young, healthy men in a two-day study with a crossover design.

They were randomized to perform 1 hour of endurance exercise on an ergometer bike or 1 hour of strenuous high-volume resistance exercise. The following week they returned to perform the opposite activity compared with week 1.

The researchers took eight blood samples from the participants before and immediately after the exercise and during a 3-hour recovery phase.

The researchers analysed the blood samples using advanced liquid chromatography–tandem mass spectrometry, which revealed relative levels of all the metabolites in the samples.

“The result is the changes to a long list of metabolites. Some are known, but there are also hundreds of obscure ones we know very little about. In this study, we mapped how the different types of exercise training changed these metabolites in the blood. As such, the result is not definitive, but we have created a catalogue that other researchers can explore to advance their knowledge on the effects of exercise training,” explains Christoffer Clemmensen.

Great interest in understanding how exercise training affects health

Other researchers may want to use these findings to study, for example, how endurance exercise improves certain aspects of metabolic health.

In the catalogue, researchers can identify what happens to many metabolites during a specific type of exercise and can then go ahead and probe causality to help them understand any direct relationship between a metabolite or metabolites of interest and physiological adaptations to exercise.

Newly discovered metabolites may therefore ultimately become interesting new targets or markers for given pathophysiological states, including disease.

Other metabolites may be especially associated with the muscle matrix remodelling and muscle strength of resistance exercise, and improved understanding of these metabolites may be relevant for optimizing resistance exercise and for understanding diseases such as muscular dystrophy.

“Our study has already been well received and is currently the most frequently read study on the Cell Reports website. This shows that there is plenty of interest in understanding how exercise affects our body,” says Christoffer Clemmensen.

Confirming classical biochemical signalling pathways

Christoffer Clemmensen says that he has not personally explored all the potential biological value in the catalogue of metabolites, but some information confirms what researchers already knew.

For example, the study reveals well-known nuances in how both types of exercise specifically increase energy metabolism in cells, organs and on a whole-body level.

Resistance exercise has a slightly different metabolic signature than endurance exercise, because of the anaerobic nature of this exercise modality.

“Our data confirm these classic biochemical signalling pathways. We also found that endurance exercise increases the blood concentrations of ketone bodies more than resistance exercise. Ketogenic diets are popular, and if you subscribe to such a dietary regime and believe that having elevated ketone bodies in the blood benefits health, our data emphasize that endurance exercise combined with fasting effectively increase these in the blood,” explains Christoffer Clemmensen.

Metabolites may benefit even without exercise training

The aim is for researchers to learn more about the health benefits of different types of exercise.

If researchers investigate the data more closely, they may discover that a given type of exercise may strongly regulate some specific metabolites or groups of metabolites that have not previously been noticed in the assessment of how exercise benefits human health.

Knowing which metabolites are heavily regulated by exercise will enable follow-up studies of what the metabolites could do in isolation.

Perhaps some overlooked metabolites play a key role in increasing muscle remodelling or exercise-induced improvement of learning and memory.

“These are just some of the benefits associated with exercise. The question then is what happens if we artificially increase the concentration of these metabolites in the blood without exercise. Can we achieve some of the same positive effects? We can gradually gain insight into these questions and begin to answer them. In the long term, the aim is to improve our understanding of at the molecular level why exercise is so healthy for us,” says Christoffer Clemmensen.

Plasma metabolome profiling of resistance exercise and endurance exercise in humans” has been published in Cell Reports. Several co-authors are employed at the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

The Clemmensen Group studies the biological regulation of body weight and aims at transforming molecular and physiological insights into innovative th...

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