Summary: Researchers have found that the brain chemical orexin plays a key role in deciding whether to exercise or indulge in a sweet treat. In mice, those with normal orexin levels were more likely to exercise than drink an attractive milkshake.
This finding may provide insight for developing strategies to combat obesity and promote physical activity in humans. Understanding the influence of orexin on physical activity and food intake decisions may pave the way for effective interventions targeting sedentary lifestyles.
Key Facts:
Role of orexin: Orexin helps the brain choose between exercising or eating a high-calorie snack. Mouse experiments: Mice with active orexin systems chose exercise over a milkshake twice as often as mice with lower levels. Potential applications to humans: These findings could lead to new strategies for tackling obesity and encouraging physical activity in humans.
Source: ETH Zurich
Should I go exercise or go to the cafe to enjoy a delicious strawberry milkshake?
Until now, what exactly happens in the brain when this decision is made has been a mystery to science, but now researchers from ETH Zurich have found the answer: they have 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.
Focus on Orexin
“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 plays a key role in this process. Orexin is one of more than 100 neurotransmitters active in the brain. Other chemical neurotransmitters, such as serotonin and dopamine, were discovered much earlier and their roles are largely understood.
The situation is different with orexin. Researchers discovered it relatively late, about 25 years ago, and its functions are now being gradually elucidated. Buldakov is one of the scientists who has devoted his efforts to studying orexin.
Existing knowledge cannot explain the choice
“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 eating,” the scientist 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.
Less time spent at the milkshake bar
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 wheel and half as much time at the milkshake bar as mice with their orexin system blocked. But interestingly, when the scientists gave the mice either the wheel or the milkshakes on their own, there was no difference in the behavior of the two groups.
“This means that the orexin system’s main role is not to control how much the mice move or how much they eat,” Buldakov says.
“Rather, it seems to be about making a decision 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.
Helping people who are lacking in exercise
The ETH Zurich researchers suspect that orexin may also be responsible for this decision in humans, as the brain functions involved here are known to be virtually identical in both species. “In the future, we will validate our results in humans,” says group leader Daria Peleg-Leibstein from ETH Zurich.
She led the study with Denis Buldakov, which may also include testing patients whose orexin system is restricted for genetic reasons (about 1 in 2,000 people).
These people have narcolepsy, a sleep disorder. Another possibility would be to look at people who are given drugs that block orexin, which are approved for insomnia patients.
“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, it may be possible to develop interventions that help overcome exercise barriers in healthy individuals and those with limited physical activity.
But Buldakov points out that these are important questions for scientists working in human clinical studies, whereas he and his group are focused on basic neuroscience research.
Next, he wants to understand how orexin neurons interact with other parts of the brain when making decisions like whether to exercise or snack.
About this Neuroscience Research News
Author: Marianne Lucien
Source: ETH Zurich
Contact: Marianne Lucien – ETH Zurich
Image: This image is provided by Neuroscience News
Original research: Open Access.
“Orexin neurons mediate voluntary movements that resist temptation” Denis Buldakov et al., Nature Neuroscience
Abstract
Orexin neurons mediate voluntary movement to resist temptation
Despite the well-known health benefits of physical activity, many people are physically inactive and it is unclear why they prioritise exercise over other options.
We developed a task that allowed us to study how mice freely and rapidly switch between wheel running and other voluntary activities, such as eating palatable food.
When given multiple choices, mice chose to spend a significant amount of time wheel-running without external reward and maintained this behavior even when palatable food was added as an option.
Causal manipulation and correlational analyses of desire and achievement processes revealed that this preference for wheel running is embodied by hypothalamic hypocretin/orexin neurons (HONs).
The impact of HON manipulation on wheel running and eating was highly situation dependent and was greatest in scenarios where both options were available.
Overall, these data suggest that HON activity enables the eat-or-run decision, resulting in the choice of exercise over food.
