Johns Hopkins researchers have identified nerve cells linked to feeding behaviors in mice. This discovery, they say, could lead to the development of new techniques to fight obesity in humans.
Specifically, researchers found the newly identified brain cells aid in portion control, telling the animals when to stop eating.
"When the type of brain cell we discovered fires and sends off signals, our laboratory mice stop eating soon after," explained Richard Huganir, director of the Department of Neuroscience at the Johns Hopkins University School of Medicine. "The signals seem to tell the mice they've had enough."
Researchers stumbled upon the cells while investigating the brain's learning and memory system, which is largely influenced by proteins that strengthen and weaken intersections, or synapses, between brain cells.
To learn more about synapse strength, researchers focused on the enzyme OGT, which is a biological catalyst involved in many bodily functions, including insulin use and sugar chemistry. This enzyme alters the behavior of proteins by adding a molecule called N-acetylglucosamine (GlcNAc) - a derivative of glucose.
For their study, researchers deleted the gene responsible for controlling OGT's role in the brain of adult mice. In just three weeks, researchers noticed the mice doubled in weight, largely due to fat buildup, rather than muscle mass.
Monitoring feeding patterns of the mice revealed that even though those missing OGT ate the same number of meals - 18 a day - they binged on food at each meal and ate more calories. However, when on a restricted diet, the mice no longer gained weight, suggesting the absence of OGT interferes with the animals' ability to sense when they were full.
"These mice don't understand that they've had enough food, so they keep eating," added Olof Lagerlöf, graduate student at Johns Hopkins Medicine.
Researchers then measured the chemical and biological activity of OGT-negative, or non-firing, brain cells. This showed that the number of incoming synapses on the cells were three times fewer than those of normal cells.
"That result suggests that, in these cells, OGT helps maintain synapses," Huganir explained. "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."
To confirm their findings, researchers stimulated the cells with a beam of blue light, showing that the cells fired and sent signals to other parts of the brain. In turn, the mice decreased the amount they ate in a day by about 25 percent.
Furthermore, researchers found that the activity of OGT is in part affected by glucose, which is needed to produce GlcNAc and generally increases after meals. Specifically, they found that by adding glucose to nerve cells, the level of proteins with GlcNAc increased proportionally.
"There are still many things about this system that we don't know," Lagerlöf concluded. "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."
Their findings were recently published in the journal Science.
