The Mysterious Interior World of Exercise

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When we exercise, far-flung parts of our bodies apparently communicate with one another, thanks to tiny, particle-filled balloons that move purposefully through the bloodstream from one cell to another, carrying pressing biochemical messages, according to an important new study of the biology of exercise.

The study helps to clarify some of the body-wide health effects of working out and also underscores just how physiologically complex exercise is.

For some time, scientists have suspected that the body’s internal organs are as gossipy and socially entangled as any 8th-grade classroom. It is thought that, under the right conditions, fat cells chat with muscle cells, and muscle cells whisper to brain cells and everybody seems to want to be buddies with the liver.

These interactions are especially abundant during exercise, when continued movement demands intricate coordination of many different systems within the body, including those that create cellular energy.

But the precise mechanics of how different parts of the body communicate during exercise (or at other times) have remained surprisingly mysterious. Scientists have shown that many tissues pump out hormones, such as insulin, and other proteins that move through the blood and jump-start physiological processes elsewhere in the body.

But these actions do not explain all of the seeming coordination between organs during exercise.

So recently, an international group of scientists from the Garvan Institute of Medical Research in Sydney, Australia, and other institutions began to consider vesicles.

Vesicles are microscopic globules within cells that contain tiny bits of biological material. Released into the blood, they once were thought to hold cellular garbage, as if the cells were heaving out their trash.

But scientists now know that vesicles also can contain useful matter, including tiny amounts of genetic material and proteins that convey biological messages to other cells.

Some researchers have speculated that exercise must cause an upsurge in such vesicles, resulting in inter-body communications that allow the body to keep moving.

But that idea had remained speculative until, for the new study, which was published this month in Cell Metabolism, the Australian scientists and others applied new technologies to the blood of exercising people.

They began by inserting tubes into the thighs of 11 healthy men and drawing blood from their femoral arteries. Then they had them ride a stationary bicycle for an hour at an increasingly strenuous pace, while they continued to draw blood. The men then rested for four hours, after which the scientists drew more blood.

The researchers next used sophisticated new sampling techniques to quantify the proteins and vesicles in the men’s blood.

And they noted striking differences before, during and after exercise. They found that about 300 types of protein-containing vesicles grew more common during exercise, and then largely disappeared after four hours of rest.

The majority of these proteins were already known to be important for metabolism and the body’s ability to regulate energy. But they had not previously been found in people’s bloodstreams during exercise.

It wasn’t clear from this sampling, though, where these vesicles and their proteins went within the body and what happened when they arrived.

So the scientists subsequently turned to laboratory mice, having some run and others remain sedentary.

They carefully isolated vesicles from the blood of both groups of animals, added a fluorescent marker to make the vesicles glow, injected them into the bloodstreams of other mice, and tracked where the glowing little bubbles went.

Most of the vesicles from the runners made a beeline for the animals’ livers, the scientists found, directed by biological signals that were not obvious but insistent.

This journey made biological sense, the scientists realized, since the liver helps to make energy during exercise.

When the scientists next added vesicles from the blood of the running mice directly into liver cells isolated from other mice, they watched as the vesicles’ exterior walls dissolved and their protein payload became absorbed into the liver cell, its biochemical message effectively delivered.

In essence, the scientists had found that exercise prompts the creation of vesicles that somehow know to head for the liver and tell it to ramp up energy production.

“This study reveals a huge amount of complexity in the circulating blood during exercise that we might have previously underestimated,” says Martin Whitham, a biologist at the Garvan Institute who, with his fellow Garvan researcher Mark Febbraio, led the new study.

The results also provide some new insights into how exercise pervasively affects our metabolisms, Dr. Whitham says. It has not been altogether clear before, for instance, how the liver knows that exercise is underway and that cells far, far distant from that organ need energy. This study provides added clarity about that issue.

Still, many questions remain, Dr. Whitham says, including what specific tissues are creating these vesicles and what else the little bubbles probably contain, including portions of genes or even bits of fat that could convey their own unique messages to other cells.

But the fundamental message of the findings is that our bodies contain a different interior world when we move than when we do not.