Scientists stumble on nerve cell that tells mice when to stop eating

When the researchers turned off the function of the nerve cell, the weight of laboratory mice doubled in just three weeks(Credit: Johns Hopkins University)

Obesity is a big health problem, affecting more than one third – or 78.6 million – adults in the United States, and costing more than US$140 billion dollars to treat every year. A new breakthrough in our understanding of how the brain tells the us that we're full could one day lead to all new tools for tackling the widespread condition. The researchers made the discovery by chance while studying learning and memory systems, instead identifying a new nerve type responsible for controlling appetite in mice.

The team of scientists, made up of researchers from the Johns Hopkins University School of Medicine, weren't actually looking at appetite when the new discovery was made. The study originally focused on learning and memory systems in the brain. More specifically, the researchers were focused on synapse strength, studying proteins that cause the intersections in the brain to become stronger or to weaken.

In the course of the study, an enzyme called OGT was studied in detail. Involved in numerous bodily functions including sugar chemistry and making use of insulin, OGT adds a derivative of glucose called N-acetylglucosamine (GlcNAc) to proteins, altering their behavior in the process.

In order to learn more about the role of OGT in the brain, the researchers removed the gene that codes for it from the primary nerve cells of the cortex and hippocampus of mice. The effects of this were quickly apparent, with team lead Olof Lagerlöf noticing a doubling in the rodent's weight over a period of just three weeks. Upon inspection, the team found that the weight gain was due to new build-ups of fat, not muscle.

Observing the mice, the team discovered that while the number of meals that the OGT deprived rodents was the same, the amount of time they spent eating, as well as the amount of calories they consumed, was increased. The fact that the weight gain stopped once the mice were put on a restricted lab diet strongly suggests that the mechanism that told the animals when they've eaten enough food was no longer functioning as it should.

These findings led the researchers to move their focus to the hypothalmus of the brain, which is known to control things such as sleep, metabolism and, most importantly, feeding. Looking closely, they observed that OGT was missing from nerve cells in the region.

Examining background electrical activity related to the chemical and biological activity of the OGT-deprived cells, the researchers were able to determine that number of incoming synapses on the cells had fallen dramatically, with three times as few present when compared to cells with OGT.

The team believes that the number of incoming synapses in the OGT-negative cells is so low that they're unable to fire, and that it's those cells that are usually responsible for telling the animal that it has consumed enough food. Without OGT, the mice simply didn't get the message that they were full.

The team successfully tested the theory by genetically manipulating the region's nerve cells, adding light-stimulated proteins. When a blue beam was shone on the cells, they fired, sending signals to other parts of the brain, causing the mice to lower the amount they were eating by some 25 percent a day.

While the research is in the early stages, it could one day lead to a new way to control appetites and ultimately, to tackle obesity. Of course, there's a lot of work to do before that could happen, including investigations involving human patients, which will allow scientists to confirm that the same or similar mechanisms exist in our bodies.

"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," said Lagerlöf.

The findings of the study were published in the journal Science.

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