Protein linked to muscle development could be new atrophy treatment target
Researchers have identified a protein that’s critical to the development of skeletal muscle mass and strength and the tissue’s ability to metabolize glucose. They say their findings may lead to treatments for the muscle wasting that can occur in disease and as a result of aging.
Skeletal muscles are necessary for producing movement, sustaining body posture and position, maintaining body temperature, storing nutrients, and stabilizing the joints. With training, skeletal muscle can be significantly improved, however, aging and extended periods without exercise can lead to wasting, otherwise known as atrophy.
Two types of fibers make up skeletal muscle: ‘slow’ (or type 1) and ‘fast’ (type 2a, 2x and 2b). Type 1 fibers have a slow contraction speed and fatigue resistance (think long-distance endurance activities like marathon running), whereas type 2 fibers are prone to fatigue but have a high contraction speed and strength (sprinting or weightlifting). From a metabolic standpoint, type 1 and type 2a fibers consume more oxygen.
In a new study, researchers from the Tokyo Metropolitan University took a deep dive into how skeletal muscle mass and strength are regulated, including the metabolic processes that drive it, and discovered the important role played by the protein Musashi-2 (Msi2).
Msi-2 is an RNA-binding protein that regulates genes involved in cell development and differentiation, although its function differs between organs. Originally, it was discovered in neural cells, as an essential factor for normal brain development. Recently, Msi2 was found in skeletal muscle cells and involved in forming muscle tissue, called myogenesis.
The researchers took calf muscle tissue samples from mice – those who’d had the Msi2 gene knocked out and those who hadn’t – and isolated the myofibers, the cellular elements that muscle tissue is made of. They found that the muscles of the Msi2 knockout mice had significantly reduced mass, less contractile strength and a whitish color instead of the normal red. Muscle tissue’s red color comes from the type 1 fibers, which are rich in mitochondria and myoglobin, an iron- and oxygen-binding protein.
Examining the tissue under a microscope, the researchers saw that the reduced mass was due to a decreased number of type 2a fibers. They also found that the muscles of the Msi2 knockout mice metabolized glucose less effectively, similar to what happens in diabetes. Skeletal muscle is the primary tissue for maintaining whole-body glucose control, where insulin facilitates glucose uptake from the circulation into the muscles to be used as an energy source.
From their findings, the researchers concluded that Msi2 regulates proteins associated with glucose metabolism and controls the proportion of different muscle fiber types in skeletal muscle tissue.
“The mice lacking Msi2 have fewer type 2a fibers and show muscle atrophy as well as decreased strength in soleus [calf] muscles,” said the researchers. “Even though glucose transport capacity was not changed significantly, total glucose disposal capacity in skeletal muscle was decreased by the loss of muscle mass in Msi2 KO [knockout] mice.”
The researchers say their findings may lead to therapies targeting type 2a muscle fibers to combat muscle atrophy and develop ways of improving muscle strength.
The study was published in The FASEB Journal.