Intensive exercise boosts communication between skeletal muscles and fat tissue, fine-tuning metabolism and improving performance, research in mice and humans suggests. The finding may lead to new treatments for metabolic diseases associated with aging and obesity.
Researchers in Brazil have discovered that aerobic exercise triggers the release of signaling molecules into the bloodstream that free up more energy for use by the muscles.
Previous research has found that aging and obesity impair the production of these signaling molecules, known as microRNAs. This increases the likelihood of metabolic diseases, such as diabetes and dyslipidemia.
The good news is that exercise may help ward off these conditions by stepping up the production of certain microRNAs.
The new research appears in the journal Proceedings of the National Academy of Sciences of the United States of America.
Marcelo Mori and his colleagues at the University of Campinas Institute of Biology in São Paulo, Brazil, collaborated on a series of experiments with researchers at the University of Copenhagen in Denmark and Harvard University in Cambridge, MA.
They started by putting mice on a treadmill for 60 minutes per day for 8 weeks. As the mice became fitter, the researchers increased the speed and slope of the treadmill.
At the end of the training program, the researchers found a significant increase in the production of a protein called DICER in the animals’ fat cells. This increase correlated with reductions in the bodyweight of the mice and the amount of visceral fat in their abdomens.
DICER is an enzyme that allows fat cells, or adipocytes, to make microRNA signaling molecules. These in turn make more energy available to the muscles.
When the scientists repeated the experiment with genetically modified mice that were unable to make any DICER in their fat cells, the mice did not benefit as much from the training program.
“The animals did not lose weight or visceral fat, and their overall fitness did not improve,” says Mori.
Fat cells in the genetically modified mice failed to supply their muscles with the extra metabolic fuel they needed during strenuous exercise.
Without DICER, says Mori, fat cells actually consume more glucose during exercise, leaving less fuel for muscles. This can lead to hypoglycemia or low blood sugar levels. In athletes, this can limit their performance.
In human volunteers who underwent 6 weeks of high-intensity interval training, the researchers recorded a fivefold increase on average in the amount of DICER in their fat tissue.
Exercise boosted DICER levels in both younger participants, whose average age was 36, and older participants, whose median age was 63. However, there was a considerable variation between individuals, which could help explain why some people benefit from exercise more than others.
To confirm that fat and muscle were communicating via signaling molecules in the bloodstream, the researchers injected blood serum from a mouse that had undergone the exercise program into a mouse that had not.
This infusion of serum from a fit mouse increased production of DICER in the recipient’s fat tissue.
“This finding suggests trained individuals have one or more molecules in their bloodstream that directly induce a metabolic improvement in adipose tissue,” explains Mori.
“If we can identify these molecules, we can investigate whether they also induce other benefits of aerobic exercise, such as [improving heart health],” he adds. “Moreover, we may think about converting this knowledge into a drug at some stage.”
The team have already taken a step in this direction by narrowing the field to one particular microRNA molecule called miR-203-3p.
They showed that when muscles have used up all their own glucose stores during prolonged exercise, miR-203-3p signals the fat tissue to make more fuel available.
“We found this metabolic flexibility to be essential to good health as well as performance enhancement,” says Mori.
Intriguingly, their previous research in mice has found that caloric restriction also increases the production of miR-203-3p.
Evidence from animal research and a few studies in humans suggests that tightly restricting calorie intake — for example, through intermittent fasting — may help stave off conditions associated with aging, such as diabetes and heart disease.
In muscle cells, a molecular sensor called AMPK is activated when the cells consume large amounts of ATP, which is the fuel that powers all the cells’ activities.
AMPK activation is known to play a role in the metabolic benefits of both caloric restriction and aerobic exercise.
In their latest series of experiments, the researchers showed that aerobic exercise activated AMPK in the muscle and fat cells of mice. This in turn increased the production of DICER in fat cells to release extra energy supplies.