Scientists Discover Protein’s Key Role in Regulating Muscle Mass and Metabolism
Researchers from Tokyo Metropolitan University have made a groundbreaking discovery regarding the regulation of muscle mass and metabolism. They have identified a protein called Musashi-2 (Msi2) that plays a crucial role in these processes in skeletal muscle.
The researchers conducted a study on mice with the Msi2 gene knocked out. They observed that these mice had reduced muscle mass due to a decrease in the number of type 2a muscle fibers. Additionally, the levels of myoglobin and mitochondria, both vital for energy production, were also significantly reduced. These findings are particularly significant because type 2a muscle fibers are highly responsive to training and are associated with various illnesses. Understanding their regulation could lead to the development of new therapies.
The ability of skeletal muscle fibers to adapt and respond to various stimuli is truly fascinating. Through training, we can enhance muscle mass, strength, and endurance. However, with age or prolonged periods without exercise, muscles can undergo atrophy, leading to a range of health issues. Despite extensive research in this area, scientists have yet to fully comprehend the mechanisms behind the regulation of muscle mass and strength.
Assistant Professor Yasuro Furuichi and his team at Tokyo Metropolitan University have made significant progress in unraveling this complex puzzle. In their previous work, they discovered that Musashi-2 (Msi2), a protein primarily found in nerve cells, is also expressed in skeletal muscle tissue. Interestingly, the expression of Msi2 in muscle tissue decreased during muscular atrophy. With the suspicion that Msi2 had a specific role in the development of muscle fibers, the researchers embarked on a more detailed investigation.
The team first isolated muscle fibers from mice, separating them from nerves, blood vessels, and fat cells using enzymes. Through analysis, they confirmed that Msi2 was indeed expressed by the muscle fibers themselves. Additionally, they discovered that Msi2 was most strongly expressed in type 1 or slow muscle fibers, which have greater endurance but less explosive power compared to type 2 or fast fibers.
To further examine the significance of Msi2, the researchers studied mice in which the gene coding for this protein was artificially depleted. These mice exhibited significantly reduced mass in their calf muscles, which appeared whitish in color and had decreased strength. Microscopic examination of the muscle fibers revealed that the decrease in mass was primarily due to a decline in the number of type 2a fibers, which combine elements of both fast and slow fibers. Additionally, the Msi2 knockout mice showed impaired sugar metabolism akin to diabetes. Moreover, they exhibited decreased levels of myoglobin and mitochondria, both essential for energy production. Interestingly, the researchers were able to rectify these issues by reintroducing Msi2 specifically into fast fibers, which restored myoglobin and protein markers for mitochondria. These findings highlight the role of Msi2 in regulating proteins associated with sugar metabolism and effectively controlling the proportion of different muscle fiber types.
Given that type 2a fibers are particularly responsive to training and susceptible to atrophy with age, this breakthrough provides valuable insights into their regulation. This information can pave the way for the development of targeted therapies to combat muscle decline and improve muscle strength through tailored training regimens.
The study was supported by the FOREST Program of the Japan Science and Technology Agency, a Tokyo Metropolitan Government Advanced Research Grant, and a TMU Strategic Research Fund for Innovative Research Project. The researchers’ findings significantly contribute to our understanding of muscle development and have the potential to revolutionize the way we approach muscle-related health issues.
In conclusion, the discovery of Musashi-2 protein’s role in regulating muscle mass and metabolism represents a major breakthrough in the field of skeletal muscle research. By shedding light on the mechanisms underlying muscle fiber development and function, this study opens up new avenues for therapeutic interventions and training techniques to enhance muscle strength and combat muscle-related health conditions.
Source: https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202300563R
