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Muscles, oxygen and energy: why FIH is the key

The levels of the enzyme FIH in our muscles determine how efficiently our muscles use oxygen to create energy, scientists have found

When you exercise, your muscles consume oxygen to produce energy, until the level of oxygen drops below a particular threshold. When this happens energy is generated through a process called anaerobic metabolism, which does not require oxygen. However, this leads to the production of lactic acid and eventually exhaustion and cramping. 

The key to how and when that switchover takes place is the enzyme FIH (Factor Inhibiting HIF) scientists have found. The finding is of potential significance to elite athletes, who have been found to have higher levels of FIH in their muscles than others. 

"We've discovered that the muscles regulate oxygen consumption in a very precise way using the oxygen-sensitive enzyme FIH," says principle investigator Professor Randall Johnson at the Department of Cell and Molecular Biology, Karolinska Institutet. "The enzyme makes sure that the muscles can use a more effective oxygen-based metabolism for as long as possible and then promotes a very quick transition to anaerobic metabolism."

Using mice in which the production of the enzyme was blocked, the researchers found that mice lacking FIH in their muscles require more oxygen than normal when exercising.

"We were able to show that without FIH, the muscles use much more oxygen than is otherwise the case," says Professor Johnson. "This could be of great significance to elite athletes, who, according to an earlier study of ours, have uncommonly high levels of muscular FIH."

FIH was discovered over ten years ago, but until now no one has understood its exact function. FIH is found in all the body's cells and tissues, but is 50 to 100 times more abundant in the muscles than in any other part of the body. The findings can now open the way for new forms of metabolism-affecting drugs.

"No one's entertained the idea of developing a drug that affects FIH before, but I think our study will lead to greater examination of that possibility," says Professor Johnson. "Here you're able to affect the metabolism itself, perhaps mainly in the muscles, but possibly in other parts of the body too. This can be important in other contexts, such as diabetes and obesity."

The study is published in the scientific journal Cell Metabolism.

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