Can a new mouse study lead to a breakthrough in understanding why people overeat?
While there are many people espousing the theory that diets are all about calories, recent accidental finding at John Hopkins lends more credence to those who think that hormones play a bigger role in appetite regulation, and may have a big impact in obesity research.
While doing a mouse study on a different brain topic, Dr. Richard Huganir and Dr. Olof Lagerlöf deleted the gene that codes for the enzyme OGT (O-GlcNAc transferase) in the hippocampus and cortex in lab mice. This enzyme is involved in many different body functions, including those involving sugar and insulin in the body. They noticed the mice doubled in weight in three weeks. Digging in, the team determined that the change had interfered with the rodents ability to determine they were satiated.
“These mice don’t understand that they’ve had enough food, so they keep eating,” Lagerlöf is quoted in the Hopkins news release. The findings were published yesterday in the Journal Science.
The hippocampus and cortex aren’t areas generally known to be involved in satiation in mammals. The researchers looked for changes elsewhere in the brain, particularly in the hypothalamus, which is generally the area known to control metabolism. They found a small subset of nerve cells within the paraventricular nucleus where OGT was missing. The postulation is that the OGT helps maintain synapses.
Additionally, since the researchers new that glucose was needed to produce a molecule called N-acetylglucosamine (GlcNAc), which is acted upon by OGT, they did some initial lab work and measured low levels of GlcNAc-decorated proteins in cells of mice that hadn’t eaten in a while.
“There are still many things about this system that we don’t know,” says Lagerlöf, “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.”
The work was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, The National Heart, Lung, and Blood Institute, and the National Institute of Neurological Disorders and Stroke.
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