How the Brain Regulates That We Don’t Overeat

Overeating

The pre-Christmas season in particular offers plenty of reasons to indulge. But when do we know it’s enough? And how exactly does the body control the feeling of fullness? Neuroscientists at the University of California, San Francisco (UCSF), in the USA, investigated this using mice. They were able to observe in real-time which brain regions and specific neurons are involved, realizing that it should not take seconds.

It is already known that the vagus nerve in the intestine can recognize how much food and nutrients have been consumed. The vagus nerve transmits this information via electrical signals to a small region in the brainstem, believed to influence when mice and humans stop eating. This region, called the Nucleus Tractus Solitarii (cNTS), contains neurons of the prolactin-releasing hormone PRLH, associated with appetite suppression, as well as GCG neurons that stimulate the production of peptides mimicked by medications like Wegovy, known as a weight loss injection. Studies on anesthetized animals have shown that both types of neurons become active in response to stomach filling.

Strong Signals From the Mouth

Now, researchers led by neurobiologist Zachary Knight have developed a new methodology, as reported in the journal Nature. They implanted light sensors in the mouse brains to indicate neuron activity. Then, they fed the mice with various types of solid and liquid food to see how and when each group of neurons responded. The recordings showed that the activity of GCG neurons increased in the minutes after a mouse started eating. The intake of food or even air into the stomach had the same effect, indicating that these neurons use stomach expansion to signal a feeling of fullness.

PRLH neurons behaved somewhat differently. As in previous research, the team found that infusing food into the stomach could activate these cells. However, when the animals were allowed to eat normally, the neurons responded much more strongly. This suggests that PRLH neurons react differently depending on whether the signals come from the mouth or the intestine, indicating that signals from the mouth override those from the intestine, says Knight.

The Factor of Time

Once the animals began licking the food, the neurons started firing and were deactivated once they stopped licking. To find out what exactly triggers these neurons, the researchers fed mice fat, sugar, calorie-free sweeteners, and water. The first three substances triggered the activity of PRLH cells within seconds, but not water. This reaction suggests that taste is “a critical factor that activates cells during feeding,” says Truong Ly, who was involved in the study, to Science News.

The nerve cells also seem to use taste signals to control how quickly one eats, according to the researchers. The results suggest that the two types of neurons “coordinate feeding behavior on two different timescales, from the very fast coordination of each bite and lick, to the longer scale satiety” says Knight. “Signals from the mouth control how fast one eats, and signals from the intestine control how much one eats.”

Eating as a Balancing Act

He and other experts emphasize that other brain regions and cells are likely involved in these behaviors. There are about 20 types of neurons in the cNTS, many of which still need to be precisely characterized. Although it is known that signals from the intestine are transmitted to this region via the vagus nerve, it is unclear how PRLH neurons receive information from the mouth, how they balance information from the mouth and stomach, and how they could regulate eating behavior from second to second.

In any case, eating speed is a balancing act, says Knight. One signaling pathway says, “this is delicious, I’m going to eat more of it,” he says. “But at the same time, there’s this [other neuronal system that] says: ‘Wait a minute, that has lots of calories, slow down a little bit.‘” What applies to mice is likely to apply to humans as well. After all, these neural circuits are generally well-conserved in both species. The work certainly raises further questions about the brain networks involved in eating and what goes wrong in the case of overeating. Enjoy your meal!