Science has just taken a giant step towards ending obesity. Or at least, for now, obesity in mice. Columbia scientists have found specialized neurons in the brains of these rodents that would be responsible for ordering them to stop eating.
We wouldn't be talking about tricking the brain, or a false feeling of fullness, but something more akin to complete brain reasoning. "These neurons are located in the brainstem, the oldest part of the vertebrate brain, and are different from any other neuron involved in regulating satiety," says Alexander Nectow, a physician-scientist at the Vagelos College of Physicians and Surgeons at Columbia University, who led the research along with Srikanta Chowdhury, a research scientist in Nectow's lab.
"Brain neurons typically limit their functions to detecting the food we eat, how full the intestine is, or what nutrients we get from it. But these neurons we have discovered are special because they seem to integrate all this data and much more," Nectow points out.
The decision to stop eating is a common phenomenon. "Every time we sit down to eat, at some point, we start to feel full, until we reach a point where we think: well, that's enough," says Nectow. But how does the brain know when the body has had enough and how does it act based on that information to stop eating?
Other researchers had previously traced the cells responsible for this decision-making to the brainstem, but the clues ended there. In the study just published in the journal Cell, Nectow and Chowdhury, however, implemented new single-cell techniques to observe this region of the brain and discern different types of cells that, until now, had been difficult to distinguish from each other.
These cells, which had not been previously recognized, had characteristics similar to other neurons involved in appetite regulation. "So we asked ourselves: 'what are these neurons for?'" Nectow says.
To see how they influenced feeding, the researchers designed a system to activate and deactivate them with light. When the neurons were activated, the mice ate much smaller portions. And if they were activated more intensely they stopped eating much faster. "They not only order an immediate stop, but also help the mice gradually decrease their food intake," says Chowdhury.
The researchers also analyzed how other food circuits and hormones affected the neurons. And thus, they discovered that these neurons were silenced by a hormone that increases appetite, but could be activated by a GLP-1 agonist, a class of drugs that are now popular for treating obesity and diabetes.
The experiments revealed that these neurons helped track every bite the mice took. "Basically, they can smell the food, see it, feel it in their mouth, in their intestine, and interpret all the intestinal hormones released in response to ingestion," explains Nectow. "Ultimately, they use all this information to decide when it's enough."
Although these specialized neurons were found in mice, Nectow says that their location in the brainstem, a part of the brain that is essentially the same in all vertebrates, suggests that it is very likely that humans have the same neurons.
"We believe it is a new and important starting point for understanding what it means to feel full and how to decide to end a meal," Nectow adds, hoping that "it can be used in obesity therapies in the future."