U.S. Department of Health and Human Services

Identification of exercise molecule that promotes physical endurance

Researchers discovered that musclin, a protein released by skeletal muscle in response to physical activity, enhances exercise capacity in mice.  The benefits of exercise are numerous and varied, but how these benefits are achieved at a molecular level remains poorly understood.  Skeletal muscle releases proteins, called myokines, and understanding the activity of myokines could lead to new therapies that provide the benefits of exercise.  In this study, scientists focused on the relationship between physical activity and a previously discovered myokine named musclin.  To determine whether or not musclin was associated with exercise, they looked at the levels of musclin in a group of mice that exercised on a treadmill daily in comparison to a sedentary group.  In addition to finding increased levels of musclin in the muscle of the active mice, musclin was increased in the mice’s blood, suggesting that it could have both local and systemic effects.

To identify the effects of exercise-induced musclin, the scientists genetically engineered mice to lack musclin.  Compared to mice with musclin, the mice without the protein showed less physical endurance; they tolerated less time, distance, and overall workload on the treadmill.  When these mice were given musclin though an infusion, they increased their exercise to normal levels.  This demonstrated that musclin was responsible for the differences in physical endurance, and that musclin has potential as a therapeutic to increase exercise tolerance, making it easier for people to exercise.  Disruption of musclin also altered the oxygen consumption of the mice during exercise and the size of mitochondria—the energy powerhouse of the cell—in the mice’s muscles, revealing how musclin affects the production of energy in the muscles. 

This study showed that levels of musclin are increased in mouse skeletal muscle in response to exercise, and that loss of musclin decreases exercise endurance and oxygen consumption.  Importantly, the scientists showed that human muscle cells in the laboratory have musclin, but additional research will be needed to establish whether human musclin acts in the same way as the mouse version.  By finding a link between musclin and physical activity, this study identifies musclin as a potential therapeutic to help people receive the benefits of exercise.

Subbotina E, Sierra A, Zhu Z, Gao Z, Koganti SR, Reyes S, Stepniak E, Walsh SA, Acevedo MR, Perez-Terzic CM, Hodgson-Zingman DM, and Zingman LV. Musclin is an activity-stimulated myokine that enhances physical endurance. Proc Natl Acad Sci USA 112: 16042-16047, 2015.​​​