summary: Researchers have developed techniques to identify and track cell-secreted molecules, often called motility factors or excelkines, that are produced during physical activity.
Their study found about 200 different proteins whose presence in the blood changed with exercise. Strikingly, a little-understood type of cell, named after the protein receptor Pdgfra, exhibits pronounced responses to exercise, suggesting complex interactions across many tissues.
The researchers also found that only hepatocytes secrete a carboxylesterase protein after exercise, and that artificially increasing this in mice improved metabolic health and endurance.
Important facts:
- Nearly 200 movement-related proteins have been identified and shown to have a wide range of effects on different tissues.
- The ‘Pdgfra’ cells found in many tissues were surprisingly responsive to exercise, indicating that more extensive studies are needed.
- Mice engineered to secrete exercise-related proteins showed resistance to weight gain and improved endurance.
sauce: Stanford
Researchers have long been fascinated by the possibility that exercise can cause different cells in the body to produce molecules beneficial to human health, said Jonathan Long, assistant professor of pathology at 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 article demonstrates that exercise modifies myriad changes in protein secretion by 21 different cell types in mice. This work also produced 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 a poorly understood class of cells named after specific protein receptors (Pdgfra) and 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 even more surprised to find that hepatocytes, and only hepatocytes, 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 Pdgfra cells play in different tissues and why do these cells respond to exercise? Potentially important anti-inflammatory and other beneficial effects on the heart, immune system and brain? change?
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.”
About this exercise and news of neuroscience research
author: Catherine Miller
sauce: Stanford University
contact: Catherine Miller – Stanford University
image: Image credited to Neuroscience News
Original research: open access.
“Whole-organism, cell-type-specific secretome mapping in exercise training in miceBy Weiwei et al. cell metabolism
overview
Whole-organism, cell-type-specific secretome mapping in exercise training in mice
There is great interest in identifying blood-derived factors that mediate tissue crosstalk and function as molecular effectors of physical activity. While previous studies have focused on individual molecules or cell types, whole-organism secretome responses to physical activity have not been assessed.
Here we used a cell-type-specific proteomics approach to generate a 21-cell-type, 10-tissue map of the secretome regulated by exercise training in mice.
Our dataset identifies over 200 cell type-secreted protein pairs that are regulated by exercise training, the majority of which have not been previously reported. PDGFRAThe -cre labeled secretome was the most responsive to exercise training.
Finally, we show the anti-obesity, anti-diabetic, and performance-enhancing effects of proteoforms of intracellular carboxylesterases whose hepatic secretion is induced by exercise training.
