Studies in mice suggest that the brain chemical orexin plays a crucial role in helping us choose between sports and the tasty foods that tempt us wherever we go.
The findings may also help people who lack motivation to exercise.
Should I go for a workout or go to a cafe to enjoy a delicious strawberry shake? Until now, what goes on in our brains when making this decision has been a mystery to science, but researchers from ETH Zurich have found the answer.
They uncovered the brain chemicals and nerve cells that mediate this decision: the transmitter orexin and the neurons that produce it.
These neuroscientific underpinnings are relevant because many people don’t get enough exercise, and most of us have probably already decided at one or more times to skip exercise in favor of one of the many temptations of daily life.
According to the World Health Organization, 80% of adolescents and 27% of adults do not get enough exercise, and obesity is increasing at alarming rates not only among adults, but also among children and adolescents.
Orexin in the spotlight
“Despite these statistics, many people resist the ever-present temptation and get enough exercise,” says Denis Buldakov, professor of neuroscience at ETH Zurich. “We wanted to find out what in the brain helps them make these decisions.”
In experiments with mice, the researchers were able to demonstrate that orexin, one of more than 100 neurotransmitters active in the brain, plays a key role in this process.
Other chemical messengers such as serotonin and dopamine were discovered a long time ago, and their roles are largely understood. On the other hand, the situation with orexin is different. Researchers discovered orexin relatively late, about 25 years ago, and its function is now being gradually elucidated. Buldakov is one of the scientists who has devoted himself to studying orexin.
“In neuroscience, dopamine is a common way of explaining why we make some choices and avoid others,” Buldakov says, because this brain messenger is so important to our general motivation.
“However, our current knowledge about dopamine does not easily explain why we decide to exercise instead of eat,” Buldakov continues.
“Our brains release dopamine when we eat and when we exercise, but it doesn’t explain why we choose one over the other.”
To understand what might motivate them, the researchers devised a sophisticated behavioral experiment in which mice were given free reign to choose between eight different options over a 10-minute test, including a running wheel and a “milkshake bar” where they could enjoy a standard strawberry-flavored milkshake.
“Mice like milkshakes for the same reason that humans do: They’re full of sugar and fat, and they taste good,” Buldakov says.
Decisions, decisions
In their experiments, the scientists compared different groups of mice: normal mice and mice in which their orexin system had been blocked, either through drugs or by genetically modifying their cells.
Mice with normal orexin activity spent twice as much time on the running wheel and half as much time at the milkshake bar as mice with their orexin system blocked.
Interestingly, however, when scientists gave mice either the running wheel or milkshakes alone, they found no difference in the behavior of the two groups.
“This means that the orexin system’s main role isn’t to control how much the mice move or how much they eat,” Buldakov says, “but rather, it seems to be responsible for making decisions to choose one or the other when both options are available.”
Without orexin, the milkshake was strongly preferred, and the mice gave up exercise in favor of eating.
The researchers suspect that orexin may also drive such decisions in humans, as the brain functions involved are known to be virtually identical in both species.
“Now we will test our results in humans,” says group leader Daria Peleg-Lybstein of ETH Zurich, who led the study together with Denis Buldakov.
This could involve testing patients who have a genetically restricted orexin system. This applies to about 1 in 2,000 people. These people suffer from narcolepsy. Another possibility would be to look at people who are given drugs that block orexin. Such drugs are approved for patients with insomnia.
“Understanding how the brain coordinates between food intake and physical activity could help develop more effective strategies to combat the global obesity epidemic and its associated metabolic disorders,” says Peleg Leibstein.
In particular, interventions could be developed to help overcome exercise barriers in healthy people and those with limited physical activity, but Buldakov points out that these pose important questions for scientists working in human clinical studies.
He and his group are dedicated to basic neuroscience research, and next he wants to understand how orexin neurons interact with other parts of the brain when making decisions like whether to exercise or snack.
This study Nature Neuroscience.
sauce: ETH Zurich
