Drugs That Give Same Health Benefits as Exercise Could Be in the Pipeline

Exercise is a great tool for maintaining good health and managing chronic disease, but it’s not always within a patient’s ability to become more physically active. Research performed at the University of Sydney’s Charles Perkins Centre, has identified 1000 distinct molecular reactions in response exercise, which may provide the tools necessary to develop ‘exercise supplements.’

According to Professor David James, Leonard P. Ullmann Chair of Metabolic Systems at the Charles Perkins Centre, and the principal investigator in the study, “Exercise is the most powerful therapy for many human diseases, including type 2 diabetes, cardiovascular disease and neurological disorders.”

“However, for many people, exercise isn’t a viable treatment option,” said Ullmann. This means it is essential we find ways of developing drugs that mimic the benefits of exercise.”

The thousand molecular changes identified by the researchers, take place in the muscles in response to exercise. This study is the first of its kind to map out the beneficial effects that exercise has on the cells in the body, and what pathways are influenced by physical activity. The results of the research were published in the journal, Cell Metabolism.

In collaboration with research groups at the University of Copenhagen in Denmark, the University of Sydney researchers used human skeletal muscle, biopsied from four healthy men after they had performed 10 minutes of high intensity exercise.

The researchers then used mass spectrometry to study phosphorylation levels of the proteins extracted from the muscle fibers. Dr. Benjamin Parker – a co-author on the paper – found that these short bursts of intense physical activity led to over 1000 changes to the muscle proteins.

Many of the changes in protein phosphorylation state had been previously identified, but were not thought to be associated with exercise. Other research in this field has concentrated on studying only a small number of exercise-associated modifications.

Co-author of the study, Dr. Nolan Hoffman from the Charles Perkins Centre and Faculty of Science, said, “Exercise produces an extremely complex, cascading set of responses within human muscle. It plays an essential role in controlling energy metabolism and insulin sensitivity.”

“While scientists have long suspected that exercise causes a complicated series of changes to human muscle, this is the first time we have been able to map exactly what happens,” said Hoffman. “This is a major breakthrough, as it allows scientists to use this information to design a drug that mimics the true beneficial changes caused by exercise.”

In an effort to determine exactly how this data could be used in the future to develop drugs that could provide the benefit of exercise to patients, the team used mathematical and engineering-based tools. James said, “Most traditional drugs target individual molecules. With this exercise blueprint we have proven that any drug that mimics exercise will need to target multiple molecules and possibly even pathways, which are a combination of molecules working together.

“We believe this is the key to unlocking the riddle of drug treatments to mimic exercise. Our data clearly show the complexity of the response: it is not one thing, but rather the drug will have to target multiple things. Our research has provided the roadmap to figure this out,” said James.

Sources:

• Exercise in a bottle could become a reality – http://www.sciencedaily.com/releases/2015/10/151001222221.htm
• Hoffman, N., Parker, B., Chaudhuri, R., Fisher-Wellman, K., Kleinert, M., Humphrey, S., Yang, P., Holliday, M., Trefley, S., Fazakerley, D., et al. (2015). Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates. Cell Metab. http://www.cell.com/cell-metabolism/abstract/S1550-4131(15)00458-1