UF finds gene that prevents satiation in obese people


Published: Tuesday, August 1, 2006 at 6:01 a.m.
Last Modified: Monday, July 31, 2006 at 11:44 p.m.
A genetic defect could keep some overweight and obese people from feeling full, according to a recent study by the University of Florida.
Mutations in the melanocortin-4 receptor, a gene in the central nervous system that aids in regulating hunger and obesity, can block signals that tell the body when to eat and when to stop. In a study of 40 genetic mutations found in obese people, researchers discovered that 11 of them caused the receptor to behave abnormally.
The objective now is to pinpoint the molecular flaw that causes the melanocortin-4 receptor to fail, which would allowing chemists to tailor drugs to treat the problem.
"In the brain, normally the body makes multiple hormones to turn the receptor on," said Carrie Haskell-Luevano, an associate professor of medicinal chemistry and lead author of the study. "If it's on, you don't want to eat. If the body makes a hormone that blocks the reaction, it drives the desire to eat. Mutations in the receptor change the way hormones in the body interact with it."
In international studies of more than 2,000 morbidly obese patients, about 6 percent had mutations in the melanocortin-4 receptor gene.
Why the receptor helps with fullness "is a good question, one that a lot of people are trying to figure out," Haskell-Luevano said. "It's a key pathway or protein in the process that your brain regulates to make you feel full or not. There's a lot more signals, it's one of maybe 30, that have to work together."
Scientists at UF collected data from cells for more than three years, observing how mutated receptors reacted to molecules that normally tell a body it is full. Their findings were published in the online journal Biochemistry in June.
The team of researchers were pulled from the departments of medicinal chemistry; pharmacodynamics; and pathology, immunology and laboratory medicine. They designed a new molecule in follow-up to correct the melanocortin-4 receptor's defects. A patent for the molecule is on file by UF.
An estimated 30 percent of adults in the United States, or more than 60 million people, are obese, according to the Centers for Disease Control and Prevention. The CDC does not use figures for obesity in children, but it reports that about 16 percent of children and adolescents are overweight.
Because some common drugs only work with certain genetic makeups, Haskell-Luevano said the study could benefit the treatment of genetic obesity with personalized medicine.
"If you know a person's genetic makeup, you can prescribe tailored treatments to specifically fix a genetic predisposition," she said. "If you know what the problem is, you can try to fix it."

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