In a new study, researchers found a new metabolic dialogue between inflammatory cells and muscle stem cells.
They found that strengthening this metabolic crosstalk with an inhibitor of the enzyme GLUD1 fosters the release of glutamine, and improves muscle regeneration and physical performance.
This can protect against muscle trauma, ischemia, and aging.
The research was conducted by a team at VIB-KU Leuven Center for Cancer Biology and elsewhere.
Skeletal muscle is instrumental to move our body, but it is also a large reservoir of amino acids stored as proteins and it influences energy and protein metabolism throughout the human body.
The role of the amino acid glutamine has been considered central for muscle metabolism because of its abundance.
However, its precise role after trauma or during chronic muscle degenerative conditions was unclear.
In the study, the team found that upon damage or during aging, the normal levels of glutamine in the muscle decrease as a consequence of dead muscle tissue.
They identified a metabolic dialogue between the inflammatory cells arriving after injury, and the resident muscle stem cells.
This cellular crosstalk re-establishes the original levels of glutamine in the muscle and, in doing so, it prompts the regeneration of the muscle fibers.
The researchers then showed that muscle injury, ischemia, and aged-related muscle wasting are conditions characterized by reduced glutamine.
One reason for this is the loss of glutamine production by the muscle itself because of its damage.
They found that genetic tools and pharmacological drugs inhibiting GLUD1, an enzyme that metabolizes glutamine, could prevent the post-injury drop in glutamine.
This resulted in the overproduction of glutamine by inflammatory cells, named macrophages, reaching the muscle after damage.
The newly produced glutamine could be used by muscle stem cells to quickly regenerate the damaged muscle tissue.
The team found the same thing in acute as well as chronic degenerative conditions, such as aging, leading to a faster muscle functional recovery.
The finding shows glutamine as a sensor molecule whose levels in the muscle tissue control a regenerative program and suggests that GLUD1 is a therapeutic target that could enable opportunities for muscle regeneration after an acute injury or chronic degenerative conditions such as aging.
One author of the study is Prof. Massimiliano Mazzone.
The study is published in Nature.
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