Nature employs a lot of checks and balances to keep life running smoothly. For example: When an animal’s stomach is full, its brain tells it to stop eating (although you might not be able to tell from watching your dog at dinnertime). Scientists say they’ve found the exact group of brain cells responsible for that “stop eating!” message—and what happens when those cells are damaged. Their report was published in the journal Science.

Many call obesity an epidemic. But what we often overlook are the myriad factors that can lead to a person becoming and staying overweight or obese. It’s not a matter of simply deciding to eat less; genetics, gut bacteria, hormones, socioeconomic status, chemical exposure, and, now, this little bundle of brain cells, have all been implicated.

The discovery of the brain’s satiety (or fullness) center was a happy accident. A team of researchers were studying the enzymes that boost or weaken synapses, the connections between brain cells. They focused their attention on an enzyme called OGT, which is known to affect how the body uses sugar and insulin.

To find out the relationship between OGT and synapses, the researchers switched off the OGT-encoding genes in a group of adult laboratory mice. Another group of mice went about their genetic business as usual. All the mice were allowed to eat as much as they wanted.

Before the researchers even began their tests, the OGT-deficient mice had doubled in weight. As the study continued, those mice continued to expand to twice their size every three weeks. And it wasn’t muscle they were gaining; it was fat, all over their bodies.

Image Credit: Johns Hopkins Medicine

The scientists began monitoring how often and how much the mice were eating. Both groups ate about 18 meals a day, but the mice in the experimental group lingered over their food and ate more calories at every meal than their control-group counterparts. The researchers then cut the chubby mice off, limiting their diet to reasonable portions. In the absence of extra calories, the mice stopped gaining weight, which suggests that the problem lay in their satiety signaling.

"These mice don't understand that they've had enough food, so they keep eating," co-author Olof Lagerlöf said in a press statement.

The thing is, the hippocampus and cortex—the areas deprived of OGT in the experimental group—aren’t generally associated with eating. So the researchers wondered if changes had occurred elsewhere in the rodents’ brains. The researchers euthanized the mice, removed their brains, and looked at thin slices of brain tissue under a high-powered microscope. They were looking for a region with a notable absence of OGT, and they found it, in a little bundle of nerve cells called the paraventricular nucleus (PVN).

Unlike the hippocampus and cortex, the PVN is known for affecting appetite and eating. But like any part of the brain, the PVN needs healthy synapses in order to do its job, and the researchers found that synapses in the fat rodents’ PVNs were in bad shape. The OGT-deficient mice had three times fewer PVN synapses than the control group.

"That result suggests that, in these cells, OGT helps maintain synapses," co-author Richard Huganir said. "The number of synapses on these cells was so low that they probably aren't receiving enough input to fire. In turn, that suggests that these cells are responsible for sending the message to stop eating."

The researchers confirmed their theory, so they tried boosting the synapses instead of wearing them down. Sure enough, mice with strong PVN synapses decreased their food intake by 25 percent.

"There are still many things about this system that we don't know," Lagerlöf said, "but we think that glucose works with OGT in these cells to control 'portion size' for the mice. We believe we have found a new receiver of information that directly affects brain activity and feeding behavior, and if our findings bear out in other animals, including people, they may advance the search for drugs or other means of controlling appetites."