"There are so many factors that come into play," Haskell-Luevano said. "It's a very simplistic approach to say what we study in a dish (completely explains) why a person is obese. At the same time, taking it down to the simplest level is how you identify specific problems."
The melanocortin-4 receptor's link to obesity was first reported in 1997 when scientists discovered that a mouse missing the protein that turns on the receptor was obese, ate more than other mice and had developed type 2 diabetes.
Scientists then made a connection in humans, discovering that some morbidly obese children and adults had mutations in the receptor at the DNA level. Since then, about 60 separate mutations have been found, Haskell-Luevano said.
"Understanding this pathway is really important to understanding obesity," said Sadaf Farooqi, M.D., a Wellcome Trust clinician scientist fellow at Cambridge University who was part of a team of British scientists who made the connection between the melanocortin malfunction and obesity in humans. "(This study) provides more detail and it starts to put some of the pieces of the puzzle together. It's an important part of getting to the next step."
UF researchers spent three years collecting data from cells, studying how mutated receptor cells reacted to the molecules that normally stimulate the body to eat or stop eating, said Zhimin Xiang, M.D., a UF biological scientist who led the experiment. Now, researchers are preparing to study mice that have been injected with the same genetic mutations they have been observing in a dish, to see if these defects cause the animals to become obese, Xiang said.
UF scientists are also trying to understand why exercise keeps the hunger-signaling system working. Emerging evidence shows that running on a wheel seems to keep melanocortin-4 receptor deficient mice from becoming obese and diabetic, Haskell-Luevano said.
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Contact: April Frawley Birdwell
afrawley@vpha.health.ufl.edu
352-273-5817
University of Florida
31-Jul-2006