Shedding new light on why extra weight is so difficult to shed permanently, researchers have found that overeating reduces levels of a hormone that signals the feeling of fullness in the brain, potentially promoting more eating. Through earlier studies on colon cancer, Thomas Jefferson University researchers led by Scott Waldman noticed that a hormone called uroguanylin also appeared to play a role in obesity. Their studies had shown that in non-obese mice, uroguanylin would travel to the brain, where it produced a feeling of fullness. But it was unclear what happened to this signaling in the obese state. In the current study, the researchers looked at mice who were overfed, and saw that the small intestines of these mice had stopped producing uroguanylin. The receptors for uroguanylin that reside in the brain were intact, and had even increased in number, but hormone itself was no longer being made, suggesting that overeating had caused its production to shut down. However, when the animals were put on a diet, the guanylin production resumed. "What's interesting is that it didn't matter whether the mice were lean and overfed, or obese and overfed - urogaunylin production stopped in both groups of animals when they got too many calories," Waldman said. The research was published in the journal Nutrition & Diabetes. "Taken together, these experiments show that excess calories - either from fat or carbohydrates - stress small intestinal cells so that they stop producing uroguanylin, which helps people feel full after eating," Waldman said. "What we don't know is how much is too much and what molecular sensor makes that decision," he pointed out.