Obesity Control: Research Offers Clues About Curbing Appetite
March 19, 2012 – A single gene mutation is responsible for the inability of neurons to effectively pass along appetite suppressing signals from the body to the brain, according to researchers at Georgetown University Medical Center (GUMC).
When such signals aren’t effectively relayed to the correct region of the brain, the result is obesity caused by a voracious appetite.
The research, published March 18 on Nature Medicine’s website and supported by grants from the National Institutes of Health and the American Diabetes Association, suggests there might be a way to stimulate expression of that gene to treat obesity caused by uncontrolled eating.
“This is the first time protein synthesis in dendrites, the tree-like extensions of neurons, has been found to be critical for control of weight,” says Baoji Xu, the study’s senior investigator. “This discovery may open up novel strategies to help the brain control body weight.”
Xu, an associate professor of pharmacology and physiology, and his team found that a specific gene mutation in mice does not allow brain neurons to effectively pass leptin and insulin chemical signals through the brain.
These hormones, released in the human body after a person eats, are designed to “tell” the person when to stop eating.
But if the signals fail to reach correct locations in the hypothalamus, the area in the brain that signals satiety, the person continues eating.
Xu previously found that the gene in question – called Bdnf – produces a growth factor that controls communication between neurons.
“If there is a problem with the Bdnf gene, neurons can’t talk to each other, and the leptin and insulin signals are ineffective and appetite is not modified,” Xu says.
One possible strategy to fix the problem would be to produce an additional long-form Bdnf transcript using a virus-based gene therapy, Xu says. But although this kind of gene therapy has proven to be safe, it is difficult to deliver across the brain blood barrier, he adds.
“The better approach might be to find a drug that can stimulate Bdnf expression in the hypothalamus,” Xu says. “We have opened the door to both new avenues in basic research and clinical therapies, which is very exciting.”