Gainesville, Fla. -- Nearly 6 percent of morbidly obese children and adults have a genetic defect that keeps them feeling like their stomach is running on empty, no matter how much they have eaten.
Mutations of the melanocortin-4 receptor, a gene found in brain cells that play a role in regulating hunger, are the most common cause of genetic obesity. Now University of Florida researchers have determined how some of these mutations cause the receptor to miss signals from molecules that tell the body when to eat and when to put down the fork, placing scientists one step closer to finding a way to correct these defects.
In a side-by-side comparison of 40 genetic mutations, UF medicinal chemists found that 11 caused the receptor to behave abnormally, according to findings recently published in the online edition of the journal Biochemistry.
The goal is to discover the molecular glitch that causes the receptor to malfunction so chemists can make drugs to treat it, said Carrie Haskell-Luevano, Ph.D., a UF associate professor of medicinal chemistry and the study's lead author. UF researchers have already found a molecule that seems to correct one of the mutations, keeping the hunger-signaling pathway running smoothly, Haskell-Luevano said.
"If you administer these compounds, it's a potential anti-obesity agent because you feel full," Haskell-Luevano said. "On the other hand, if you have cancer or wasting disease, if you administer an antagonist that blocks or turns off the system, then you want to eat or you feel hungry.
"It directly controls the desire to eat."
About 30 percent of adults and 16 percent of children in the United States are overweight, according to the Centers for Disease Control and Prevention. Only a fraction of these people have genetic conditions or mutations that are linked to obesity, but researchers say studying genetic obesity can also help uncover clues to treating the nation's growing
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Contact: April Frawley Birdwell
afrawley@vpha.health.ufl.edu
352-273-5817
University of Florida
31-Jul-2006