What makes us decide to stop eating? Research on food regulation is prolific. We know the circuits that, once the stomach is full, suppress the sensation of hunger. But a gray area persists regarding the mechanisms that make us put down the fork! Researchers at Columbia University (New York) have just identified a group of previously unknown neurons. Sensitive to numerous signals from digestion, they are activated over a long period of time, and ultimately trigger the end of the meal. These fundamental results in mice open new therapeutic perspectives for pathologies that require regulation of eating behavior.Although we are still at the beginning, we hope that our results will have a significant impact on the medical field," says Skrikanta Chowdhury, first author of the study, in an interview for Science and FutureTheir study was published in the journal Cell.
Neurons involved in satiety
Regulating meal intake involves various brain structures.On the one hand, neurons in the forebrain, including the hypothalamus, control hunger and satiety while the hindbrain regulates meal size," explains Skrikanta Chowdhury. In particular, a small part of the hypothalamus called the "arcuate nucleus" acts as a hunger detector. It integrates hormonal information from the digestive tract and fatty tissue. "These signals generate different reactions from the hypothalamus," he adds. For example, some cells detect metabolic deficits and stimulate hunger to encourage food intake. Others, called POMC, can detect excess energy and extend the interval between meals.
Read alsoHow the hunger hormone directly affects our decision-making
The Columbia University team has identified a new cog in these circuits: neurons sensitive to the hormone CCK (cholecystokinin), which are quite different from other cells involved in regulating hunger.The brain's neurons are generally limited to detecting what is put in the mouth, how the food fills the intestine, or the nutrients obtained from the bolus,"inventories the biologist."The neurons we discovered have the particularity of integrating all this different information and much more!”
Making the decision to stop eating…
Using a new technique, the researchers analyzed the brainstem, an extension of the spinal cord in the neck, in order to discern different types of cells.This technique, called spatial transcriptomics, allows us to see cells where they are located in the brainstem and what their molecular composition looks like,” explains Alexander Nectow, co-author of the study. There, they distinguish previously unknown cells, some of whose characteristics remind them of the neurons involved in satiety.We thought, “Oh, that’s interesting. What are these neurons doing?”" recall the scientists. To understand their role, the researchers used optogenetics, a technique that allows a group of neurons to be activated or deactivated using light.When the neurons were activated by light, the mice ate much smaller meals," reports Skrikanta Chowdhury. As for the intensity of the activation, it determined how quickly the mice stopped eating.Interestingly, these neurons don't just signal an immediate stop; they help mice gradually slow down their food consumption," he enthuses.
Read alsoBrain, sleep, cancer: the 7 promises of GLP-1
But what signals do they react to? The team discerns both groups of cells and molecules that interact with CCK neurons. In particular, GLP-1; this hormone released in the intestine after food intake and which is the basis of many well-known anti-obesity drugs. In particular, it helps regulate blood sugar and other physiological processes.We found that newly discovered neurons in the brainstem can detect GLP-1 in the bloodstream," says Skrikanta Chowdhury. It causes a slow but sustained activation of these neurons, which ultimately leads to the cessation of eating.
Towards new anti-obesity drugs?
The researchers were able to identify the various signals to which this group of neurons is sensitive. These include thoughts about food, smells and visual cues, the perception of each bite, but also the bolus of food in the stomach and, more generally, the hormonal state linked to food.There is much to learn from these newly characterized neurons," weighs the author. "For example, we don't yet fully understand how these neurons integrate different aspects of signals during feeding, and to what extent the cells can adapt.“In the coming days, by integrating modern tools such as CRISPR and AI, researchers will try to shed light on the molecular and cellular foundations of this physiological process.”Whether alone or in combination with other types of management, these results could pave the way for the clinical regulation of eating behavior and potentially for other medications to combat excess weight." he concludes.
English 
French