The body, we know, responds to exercise, which suggests that at some level, the body “knows” if it is exercising. Now, the body isn’t clairvoyant. It responds to exercise via physical mechanisms—and mechanisms can be hacked. Imagine: If the body could be tricked into believing it is active, even if it is sedentary, perhaps it could derive more of the health benefits of exercise. Not so much pain. More gain.

While exploring this possibility, scientists based at Leeds University identified a key biomolecular mechanism by which exercise is sensed. These scientists have found that a protein called Piezo1 in the lining of blood vessels is able to detect a change in blood flow during exercise.

Piezo1, the scientists asserted, is an “exercise sensor.” They detailed its function in mouse studies. They also indicated that Piezo1 is also found in humans, which suggests that this and other exercise sensors might lead to ways to better tune human biology. In fact, the scientists found that Piezo1 not only responds to increases in blood flow, it also responds to an experimental drug called Yoda1.

Details of this work appeared August 24 in the journal Nature Communications, in an article entitled “Piezo1 Channels Sense Whole Body Physical Activity to Reset Cardiovascular Homeostasis and Enhance Performance.”

“Mice without endothelial Piezo1 lack obvious phenotype but close inspection reveals a specific effect on endothelium-dependent relaxation in mesenteric resistance artery,” wrote the article’s authors. “Strikingly, the Piezo1 is required for elevated blood pressure during whole body physical activity but not blood pressure during inactivity.”

During physical activity—as the heart pumps more blood around the body—the Piezo1 protein in the endothelium or lining of the arteries taking blood from the heart to the stomach and intestines senses the increased pressure on the wall of the blood vessels. In response, it slightly alters the electrical balance in the endothelium and this results in the blood vessels constricting.

In a clever act of plumbing, that narrowing of the blood vessels reduces blood flow to the stomach and intestines, allowing more blood to reach the brain and muscles actively engaged in exercise.

The Leeds team, led by David Beech, Ph.D., believe that the health benefit of exercise may be linked with the fact that blood flow is being controlled to the intestinal area.

“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 Dr. Beech. “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.”

The researchers also investigated the effect of an experimental compound called Yoda1—named after the character from Star Wars—on the action of the Piezo1 protein.

They found that it mimicked the action of increasing blood flow on the walls of the endothelium that is experienced during physical activity, raising the possibility that a drug could be developed that enhances the health benefits of exercise.

“One of our ideas is that Piezo1 has a special role in controlling blood flow to the intestines,” explained Dr. Beech. “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.

“By modifying this protein in the intestines, then 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.”

The scientists are working with chemists, also based at the University at Leeds, to modify the Yoda1 molecule so it can be used on further animal studies.

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