Our mouths might help keep our hunger in check. A recent study found evidence in mice that our brains rely on two separate pathways to regulate our sense of fullness and satiety—one originating from the gut and the other from cells in the mouth that let us perceive taste. The findings could help scientists better understand and develop anti-obesity drugs, the study authors say.
The experiment was conducted by researchers at the University of California San Francisco. They were hoping to definitively answer one of the most important and basic questions about our physiology: What actually makes us want to stop eating?
It’s long been known that the brainstem—the bottom part of the brain that controls many subconscious body functions—also helps govern fullness. The current theory is that neurons in the brainstem respond to signals from the stomach and gut as we’re eating a meal, which then trigger that feeling of having had enough. But scientists have only been able to indirectly study this process until now, according to lead author Zachary Knight, a UCSF professor of physiology in the Kavli Institute for Fundamental Neuroscience. His team was able to directly image and record the fullness-related neurons in the brainstem of alert mice right as they were chowing down.
“Our study is the first to observe these neurons while an animal eats,” Knight told Gizmodo in an email. “We found surprisingly that many of these cells respond to different signals and control feeding in different ways than was widely assumed.”
The team focused on two types of neurons in the brainstem thought to regulate fullness: prolactin-releasing hormone (PRLH) neurons and GCG neurons.
When they fed mice through the stomach alone, they found that PRLH neurons were activated by the gut, as expected by prior assumptions. But when the mice ate normally, these gut signals disappeared; instead, the PRLH neurons were almost instantly activated by signals from the mouth, largely from the parts responsible for taste perception. Minutes later, the GCG neurons were activated by gut signals.
The team’s findings, published Wednesday in Nature, indicate that there are two parallel tracks of satiety in the brainstem, ones that operate at different speeds with slightly different purposes.
“We found that the first pathway—which controls how fast you eat and involves PRLH neurons—is unexpectedly activated by the taste of food,” Knight said. “This was surprising, because we all know that tasty food causes us to eat more. But our findings reveal that food tastes also function to limit the pace of ingestion, through a brainstem pathway that likely functions beneath the level of our conscious awareness.”
The second pathway, governed by the gut and GCG neurons, seems to control how much we ultimately eat, Knight added.
Mice are not humans, of course. So more research will be needed to confirm whether we have a similar system. But assuming that we do, the team’s work could have some important implications.
In recent years, for instance, there have been several newly approved obesity drugs that appear to be much more effective at inducing weight loss than past treatments, such as semaglutide (Wegovy/Ozempic). While these drugs do cause relevant physiological changes, such as slowing down digestion, it’s also thought that they affect people’s sense of fullness via the brain. This new imaging technique should allow scientists to better study how these drugs work up close, which is something that the team is already planning to do.
The lessons learned from this research could also lead to new obesity drugs, Knight said. Since PRLH neurons seem capable of switching how they respond to food-related signals, for example, it might be possible to cause this switch ourselves, a strategy that could then be used to tamp down our appetite.
“Importantly, if we can figure out how this sensory filtering works and block it—so that PRLH neurons respond to gut signals during normal ingestion—this would potentially create a potent inhibition of food intake and could be a new strategy for treating obesity. We are working on this now,” Knight said.