Scientists stumble on nerve cell that tells mice when to stop eating
Obesityis a big health problem, affecting more than one third – or 78.6million – adults in the United States, and costing more than US$140billion dollars to treat every year. A new breakthrough in ourunderstanding of how the brain tells the us that we're full could oneday lead to all new tools for tackling the widespread condition. Theresearchers made the discovery by chance while studying learning andmemory systems, instead identifying a new nerve type responsible forcontrolling appetite in mice.
Theteam of scientists, made up of researchers from the JohnsHopkins University School of Medicine, weren't actually looking atappetite when the new discovery was made. The study originally focused on learning and memory systems in the brain. More specifically, theresearchers were focused on synapse strength, studying proteins thatcause the intersections in the brain to become stronger or to weaken.
Inthe course of the study, an enzyme called OGT was studied in detail.Involved in numerous bodily functions including sugar chemistry andmaking use of insulin, OGT adds a derivativeof glucose called N-acetylglucosamine (GlcNAc) to proteins, alteringtheir behavior in the process.
Inorder to learn more about the role of OGT in the brain, theresearchers removed the gene that codes for it from the primary nervecells of the cortex and hippocampus of mice. The effects of this were quicklyapparent, with team lead Olof Lagerlöfnoticing a doubling in the rodent's weight over a period of justthree weeks. Upon inspection, the team found that the weight gain wasdue to new build-ups of fat, not muscle.
Observingthe mice, the team discovered that while the number of meals that theOGT deprived rodents was the same, the amount of time they spenteating, as well as the amount of calories they consumed, wasincreased. The fact that the weight gain stopped once the mice wereput on a restricted lab diet strongly suggests that the mechanismthat told the animals when they've eaten enough food was no longerfunctioning as it should.
Thesefindings led the researchers to move their focus to the hypothalmusof the brain, which is known to control things such as sleep,metabolism and, most importantly, feeding. Looking closely, theyobserved that OGT was missing from nerve cells in the region.
Examiningbackground electrical activity related to the chemical and biologicalactivity of the OGT-deprived cells, the researchers were able todetermine that number of incoming synapses on the cells had fallendramatically, with three times as few present when compared to cellswith OGT.
Theteam believes that the number of incoming synapses in theOGT-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 ithas consumed enough food. Without OGT, the mice simply didn't get themessage that they were full.
Theteam successfully tested the theory by genetically manipulating the region's nervecells, adding light-stimulated proteins. When a blue beam was shoneon the cells, they fired, sending signals to other parts of thebrain, causing the mice to lower the amount they were eating by some25 percent a day.
Whilethe research is in the early stages, it could one day lead to a newway to control appetites and ultimately, to tackle obesity. Ofcourse, 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 inour bodies.
"Webelieve we have found a new receiver of information that directlyaffects brain activity and feeding behavior, and if our findings bearout in other animals, including people, they may advance the searchfor drugs or other means of controlling appetites," said Lagerlöf.
Thefindings of the study were published in the journal Science.
Source: Johns Hopkins University