Understanding how different cell types respond to exercise could be a key step towards making exercise a medical reality

by Catherine Miller

Researchers say they have long been fascinated by the possibility that exercise causes various cells in the body to produce molecules that benefit human health. Jonathan LongAssistant Professor of Pathology, Stanford University.

Theoretically, if these molecules, also called motility factors or excelkines, could be identified and used for pharmacological purposes, the incidence of certain health problems such as obesity, heart disease and diabetes could be reduced, and athletic performance could be improved. It could be improved. .

But that goal remains elusive, Long says, largely because it has been impossible to isolate Excelkine from blood. “When you analyze whole blood, you can see only the most abundant substances in it, and the rest are invisible.”

But now, Long and his team have developed a new technique that can look deeper into the blood and identify cell-secreted molecules. This technique also reveals which cell types produce which molecules. This is important information for a better understanding of the role exercise plays in improving health.

And by Mr. Long’s innovative method, cell metabolism This paper demonstrates the myriad ways that exercise alters protein secretion by 21 different cell types in mice. This research was supported in part by a grant from the Foundation. Wu Tsai Human Performance Alliancealso brought some surprises.

First, the number of proteins whose presence in the blood changed in response to exercise was higher than expected. In fact, the research team found about 200 different motility factors whose expression is up- or down-regulated by 21 cell types. “This means that the effects of physical activity are very widespread across many tissues and organ systems,” Long says. “We are just beginning to understand the complexity.”

Second, the cells most responsive to exercise were poorly understood types of cells named after specific protein receptors (PDGFRA) and are found in many different tissues and organs. In fact, normal suspect cells, such as muscle, bone and liver cells, had only moderate responses by comparison, Long says. “If you really want to understand exercise responses, you can’t just focus on the muscles, bones, and other tissues involved in exercise,” he says. “We need to look broader.”

The researchers were also surprised to discover that hepatocytes (hepatocytes only) secrete several members of the carboxylesterase family of proteins after exercise. Researchers have previously focused on the functions of these proteins within cells, showing that they are beneficial for metabolic health, but have not observed a possible role in blood flow. rice field.

To better understand their role, Long’s team generated mice that secrete high levels of carboxylesterase proteins from their livers even when they don’t exercise. They found that these mice resisted weight gain on a high-fat diet and improved endurance on the treadmill. “These carboxylesterases are sufficient to confer some of the metabolic benefits of exercise without the animals themselves exercising,” says Long.

This study raises many questions that require follow-up.what role do you play PDGFRA Cells are active in a variety of tissues, so why do these cells respond to exercise? may have important anti-inflammatory and other beneficial effects on the system, brain? In humans, as in mice, levels of carboxylesterase carried in the blood change in response to exercise. mosquito?

From a basic science standpoint, Long hopes the work will advance our understanding of cell-to-cell communication. But from a 30,000-foot perspective, there’s another reason for doing this kind of painstaking research study. That is the unfulfilled promise of “exercise as medicine.”

While we know exercise can be therapeutic for many of the most chronic debilitating conditions, Long says exercise isn’t like medicine yet. That’s because most pharmaceuticals consist of well-defined molecules with well-defined mechanisms of action, pharmacokinetics and pharmacodynamics, and side effects. By contrast, none of these are clearly defined in terms of movement, he says. “In the long term, we would like to understand the molecules and cells involved in exercise at high resolution to realize exercise as medicine.”

This study was conducted in collaboration with the Molecular Athlete Program of the Wu Tsai Human Performance Alliance.Co-authors include wei wei, Nicholas M. Reilly, Shuqiao Liu, Xiaotao Shen, Jin Guo, Stephen H. Laung, Meng Zhao, Maria Dolores Moya-Gazon, Himanish Bass, Alan Shenhua Tung, Veronica L. Lee, Wentao Huang, Amanda L. Wiggenhorn, Katherine J. Svenson, Michael P. Snyder, Carolyn R. Bertozzi

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