Summary
Reduction in muscle mass is called skeletal muscle atrophy. It results from various types of stress such as starvation and injury to the nerves, and is a common consequence of aging. A recent study attempted to understand the mechanism behind the induction of skeletal muscle atrophy due to starvation and nerve damage. The authors of this study analyzed mRNAs from mouse muscles and human muscles that were regulated by nerve injuries and starvation. They also evaluated the role of ursolic acid, a natural compound found in apples, in preventing atrophy of muscles. They studied its effects on various health parameters such as fat content, blood glucose, and lipid levels. It was found that ursolic acid reduced muscle atrophy and stimulated an increase in muscle mass.

Introduction
Skeletal muscle atrophy occurs under conditions of stress, starvation, and spinal cord injuries. It leads to complications of other human illnesses like heart failure, kidney failure, diabetes, cancer, AIDS, and respiratory diseases. This disease leads to weakening of muscles, causing falls, fractures, and other respiratory infections. Patients tend to become dependent on other individuals for carrying out routine tasks. Modern medicine lacks suitable treatments and cures that can reverse muscle atrophy. Hence, the researchers of this study set out to identify such a compound that could inhibit or even reverse skeletal muscle atrophy. For this, they carried out experiments on both humans and mice, noting the mRNAs whose levels were elevated upon fasting and nerve damage. Later, they tried to find out whether these mRNAs can be inhibited by natural substances such as ursolic acid.

Methodology

  • The first part of the experiment was carried out on seven healthy adult humans with an average age of 46 years. They were made to fast for 40 hours without food, but were allowed to drink water.
  • Muscle biopsy samples were taken before and after fasting. The levels of mRNA in the skeletal muscles were then estimated. Using statistical and computational queries on an already available database of about 1,300 bioactive molecules, metformin and ursolic acid were identified as potential compounds that may inhibit skeletal muscle atrophy. Mice were administered with both these compounds before and after fasting, and their effects on muscle atrophy were evaluated.
  • To test the effect of ursolic acid on muscle atrophy resulting from nerve injury, the left hind limb muscles of mice were denervated by cutting the sciatic nerve. Ursolic acid was then administered to the mice twice daily, followed by an examination of the right and left hind limb muscles.
  • In order to test whether ursolic acid increased the muscle mass, a group of mice was fed with a diet comprising of 0.27% ursolic acid for five weeks.

Results

  • Out of more than 17,000 mRNAs assessed from human muscle biopsy samples, the levels of 281 mRNAs were elevated when the participants fasted for 40 hours. Many of them were involved in the process of catabolism.
  • Ursolic acid was found to possess maximal inhibitory actions on mRNAs whose levels were elevated during starvation. Metformin, however, possessed no such activity.
  • Furthermore, it was found that ursolic acid inhibited the muscle atrophy produced due to damage to nerves. Mice fed on a diet rich in ursolic acid were found to have a greater muscle mass than those who were fed on a normal diet. There was a decrease in fat content of the body, blood glucose, and cholesterol levels upon the administration of ursolic acid.

Shortcomings/Next steps
The levels of 281 mRNAs were found to be elevated upon fasting. The role of many of them in causing atrophy is not yet known. Hence, a decrease in their levels cannot actually be associated with reduction in muscle atrophy. If ursolic acid is to be used in therapeutics, details of its absorption, metabolism, and excretion must be studied. It is also necessary to study whether other derivatives of ursolic acid possess a higher potential than ursolic acid in the treatment of muscle atrophy.

Conclusion
Ursolic acid is an easily available natural compound, present in apple peels and many edible plants. This study confirmed that ursolic acid significantly reduced skeletal muscle atrophy, resulting from two important stress inducers, namely, starvation and muscle denervation. Thus, a new compound that can be used in the treatment and prevention of skeletal muscle atrophy has been discovered. Further clinical trials are necessary to validate its utility in humans. Another significant finding of this study is that ursolic acid can reduce body fat, and sugar and lipid levels in blood. Hence, this compound must be tested for its potential role in the treatment of diabetes and obesity.

For More Information:
mRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass
Publication Journal: Cell Metabolism, June 2011
By Steven D Kunkel; Manish Suneja
From The University of Iowa, Iowa City, Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa

*FYI Living Lab Reports Are Summaries of the Original Research.

 

 



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