No sweat: Yoda1 molecule activates the body's exercise sensor
The idea of exercise in a pill has been one that captures the heart of anyone who would rather lift their TV's remote instead of a barbell while still gaining the powerful health benefits that come from exertion. While such a pill might still be be far away, researchers at the University of Leeds in England have taken us a step closer by examining a protein they call the body's "exercise sensor" and learning how to activate it with a molecule named after a Star Wars character.
In studies using mice, the research team discovered that a protein called Piezo1 can figure out when the body is undergoing exercise. That's because when mammals are put under stress, our blood pumps stronger, putting more pressure on the walls of our blood vessels. When this happens, the Piezo1 protein kicks into gear and slightly changes the electrical charge in the endothelium, an arterial lining.
In the study, the team discovered that this caused the endothelium in the arteries that move blood from the heart to the stomach and intestines to narrow, allowing more blood to flow to the brain and to the muscles that are being put under stress by the physical activity. According to the researchers, this discovery is the first of its kind, in that it uncovers a biomolecular mechanism by which the body senses exercise. The discovery, they say, could help develop methods to deal with a range of diseases for which the physical impacts of exercise are helpful, without people actually having to exercise.
"If we can understand how these systems work, then we may be able to develop techniques that can help tackle some of the biggest diseases afflicting modern societies," said lead investigator David Beech, from the Leeds Institute of Cardiovascular and Metabolic Medicine. "We know that exercise can protect against heart disease, stroke and many other conditions. This study has identified a physiological system that senses when the mammalian body is exercising."
One such method in which the Piezo1 exercise sensor could be activated is through an experimental molecule named Yoda1, which can manipulate the protein. In their study, the researchers tested Yoda1 and found that it increased the blood flow in the endothelium in the same way as exercise and therefore could impact Piezo1.
"One of our ideas is that Piezo1 has a special role in controlling blood flow to the intestines and this is really an important part of the body when we start to think about something called the metabolic syndrome which is associated with cardiovascular disease and type 2 diabetes," said Beech.
"By modifying this protein in the intestines, perhaps we could overcome some of the problems of diabetes and perhaps this Yoda1 compound could target the Piezo1 in the intestinal area to have a functional effect. It may be that by understanding the working of the Yoda1 experimental molecule on the Piezo1 protein, we can move a step closer to having a drug that can help control some major chronic conditions."
Beech and his team will now move to the next phase of the study in which they will alter Yoda1 to be used in more animal studies.
And, while the study was performed on mice, humans also have Piezo1 in their systems, so the results could carry over. If so, treatment with Yoda1 could join other "exercise in a pill" therapies including a protein called cardiotrophin 1 (CT1) that helps the heart grow in much the same way as physical activity; a chemical compound that was shown to increase the burning of fat as well as endurance; a protein that, when suppressed, leads to more muscle mass; and a drug that tricks the body into burning fat by convincing it that it has had a meal.
The Leeds-led research has been published in the journal Nature Communications.