Enjoy the buffet, but let your brain tell you when to stop.
Richard Huganir, PhD, director of the Department of Neuroscience at the Johns Hopkins University School of Medicine, and colleagues were looking at how proteins increase the strength or weakness of the synapses that link brain cells. Synapse strength affects learning and memory, especially in the hippocampus and cortex of the brain.
They were focusing on the role of the enzyme OGT, which among other functions, is involved in the processing of insulin and sugar.
In 1984, Gerald Hart, PhD, director of the Johns Hopkins University School of Medicine's Department of Biological Chemistry and co-leader of the current study, discovered that OGT adds a glucose derivative - called N-acetylglucosamine (GlcNAc) - to proteins that affects how they behave.
In a study of adult mice, the researchers removed the gene that codes for OGT.
Removal of OGT leads to rise in fat and weight
Within 3 weeks of eliminating the gene from the primary nerve cells of the hippocampus and cortex, the mice experienced an increase in fat that doubled their weight.
A closer look at feeding patterns revealed that mice without OGT ate an average of 18 meals a day, the same as mice with OGT, but those without OGT spent longer eating their food and consumed more calories at each meal.
The weight gain halted when food intake was restricted to that of a normal lab diet.
Fast facts about obesity
- 34.9% of the US population are obese
- The 40-59 years age group is most prone to obesity at 39.5%
- Obesity cost the US $147 billion in health costs in 2008.
The researchers conclude that removing OGT from the mice also removed their ability to sense when they were full.
As coauthor Dr. Olaf Lagerlöf says: "These mice don't understand that they've had enough food, so they keep eating."
Seeking an explanation, the researchers focused on the hypothalamus, known for its role in controlling body temperature, feeding, sleep and metabolism.
OGT was found to be missing from a small subset of nerve cells within a cluster of neurons called the paraventricular nucleus. Previous research has shown that these cells are involved in the signaling process relating to appetite and food intake.
Dr. Lagerlöf then looked for changes in the levels of specific factors that might be affected by the lack of OGT.
He found no impact on most of these factors and concluded that the reason for the weight gain did not lie with the better-known appetite signals.
Lack of OGT reduces effectiveness of synapses
The next step was to look at the chemical and biological activity of the cells with missing OGT.
The team measured the background electrical activity in brain cells that do not send signals, and they found three times fewer incoming synapses on the cells, compared with normal cells.
The scientists checked this by genetically manipulating the cells in the paraventricular nucleus, to enable them to add blue light-sensitive proteins to their membranes.
They then stimulated the cells with a beam of blue light, whereupon the cells emitted signals to other parts of the brain, and the daily food intake of the mice fell by 25%.
"That result suggests that, in these cells, OGT helps maintain synapses. 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."
Finally, since glucose is needed to produce GlcNAc, the researchers looked at the impact of glucose levels on OGT activity. Glucose levels increase after meals.
When glucose was added to nerve cells in vitro, the proportion of proteins with GlcNAc increased in relation to the amount of glucose.
Moreover, examination of cells in the paraventricular nucleus of fasting mice revealed low levels of GlcNAc-decorated proteins.
The authors point out that although far more research is needed, there is evidence that glucose and OGT work together to regulate "portion size."
They believe they have found "a new receiver of information that directly affects brain activity and feeding behavior," which could eventually lead to therapies for controlling appetites.
Last year, Medical News Today reported that the hormone FGF21 plays a role in regulating the appetite for sugar.