New research from the University of Sydney reveals around 1000 molecular reactions to exercise, opening the door for drug treatments to mirror the health benefits of exercise.
Drugs that mimic the benefits of exercise could soon become a reality thanks to breakthrough research from the University of Sydney’s Charles Perkins Center.
Published in Cell Metabolism, the research exposed a thousand molecular changes that occur in our muscles when we exercise, providing the world’s first comprehensive exercise blueprint.
“Exercise is the most powerful therapy for many human diseases, including type 2 diabetes, cardiovascular disease, and neurological disorders,” said Professor David James, Leonard P. Ullmann Chair of Metabolic Systems at the Charles Perkins Center and the head of the research group that undertook the study.
“However, for many people, exercise isn’t a viable treatment option. This means it is essential we find ways of developing drugs that mimic the benefits of exercise.”
The University of Sydney researchers, in collaboration with researchers from the University of Copenhagen in Denmark, analyzed human skeletal muscle biopsies from four untrained, healthy males following 10 minutes of high-intensity exercise. Using a technique known as mass spectrometry to study a process called protein phosphorylation, co-author Dr. Benjamin Parker discovered that short, intensive exercise triggers more than 1000 changes.
The majority of changes they discovered have not previously been associated with exercise, with existing research focusing on just a small number of changes.
“Exercise produces an extremely complex, cascading set of responses within human muscle. It plays an essential role in controlling energy metabolism and insulin sensitivity,” said co-author Dr. Nolan Hoffman from the Charles Perkins Center and Faculty of Science.
“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.”
“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,” Dr Hoffman said.
With this long-term goal in mind, researchers narrowed down the therapeutic possibilities within the blueprint using mathematical and engineering-based analysis.
“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,” Professor James said.
“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 road map to figure this out.”
Reference: “Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates” by Nolan J. Hoffman, Benjamin L. Parker, Rima Chaudhuri, Kelsey H. Fisher-Wellman, Maximilian Kleinert, Sean J. Humphrey, Pengyi Yang, Mira Holliday, Sophie Trefely, Daniel J. Fazakerley, Jacqueline Stöckli, James G. Burchfield, Thomas E. Jensen, Raja Jothi, Bente Kiens, Jørgen F.P. Wojtaszewski, Erik A. Richter and David E. James, 1 October 2015, Cell Metabolism.
DOI: 10.1016/j.cmet.2015.09.001
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