Around 1-in-20 obese people have a genetic defect that makes them feel like their stomach is empty, no matter how much they have eaten. In 1997, researchers pinpointed the melanocortin-4 receptor gene as the likely culprit and since then researchers have been working on ways to correct this genetic glitch. Now, University of Florida (UF) researchers have determined how some of these genetic mutations tell the body when to eat and when to put down the fork, putting them one step closer to finding a way to correct these defects. UF researchers have already found a molecule that seems to correct one of the mutations, keeping the hunger-signaling pathway running smoothly. "If you administer these compounds, it's a potential anti-obesity agent because you feel full," said UF's Carrie Haskell-Luevano. "It directly controls the desire to eat."
While only 5 percent of obese people have genetic conditions or mutations that are linked to obesity, the researchers say studying genetic obesity can also help uncover clues to treating the nation's growing weight problem. "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."
Mutations in the receptor at the DNA level have been the subject of much study of late, and about 60 separate mutations have been found. The UF researchers are now studying how mutated receptor cells react to the molecules that normally stimulate the body to eat or stop eating. Central to this is a study with mice that have been injected with the same genetic mutations, to see if these defects cause the animals to become obese.
Another aspect of the research concerns the effects of exercise, which appear to go beyond simply burning calories. It seems that physical activity also keeps the hunger-signaling system working properly, with emerging evidence showing that running on a wheel seems to keep melanocortin-4 receptor deficient mice from becoming obese and diabetic.
Source: University of Florida
