Pigging out may seem a mental state. But some people really lack a 'lid' to their stomach. This "lid" was found to be leptin, a hormone already involved in regulating appetite.

A new research links leptin to food craving, shedding light on the way the brain controls the appetite and, ultimately, the roots of obesity. Leptin acts like a sensor for the body's energy storage. Fat tissue generates leptin which through the bloodstream reaches the brain, signaling that the body has ingested enough food. When fat deposits are fasting, leptin levels drop and the brain turns on the hunger center. But until now it was not known if the hormone acts on the brain centers linked to craving and reward.

A team led by endocrinologist Sadaf Farooqi of the University of Cambridge, U.K., investigated the issue in a 14-year-old boy and a 19-year-old girl whose bodies did not synthesize leptin. Functional magnetic resonance imaging (fMRI) delivered scanned images of the brain activity of the volunteers while fasting and after eating. While performing each type of scan, the patients watched pictures of food and nonfood items.

The subjects presented higher activation in reward-related brain centers in response to the food images, no matter if they had eaten, and they always scored the food representations as highly desirable.

After that, the subjects were treated with leptin for 7 days, and the fMRI scanning was repeated in the same situations. Now, the subjects only had higher brain activation when watching food images if they had previously been fasting, and food representations were ranked as less desirable if they had eaten.

Leptin appeared to have an important role in the brain's capacity to differentiate between the fed and fasted states. The subjects said that before the leptin shots, they permanently felt like being hungry while watching others eating. "Although leptin deficiency is not typically the cause of obesity--most obese people have normal or high levels of leptin--the study pinpoints the neural circuitry responsible for food craving," said Jeffrey Friedman, a geneticist at Rockefeller University in New York, the first to detect the role played by leptin in appetite.

"The findings are a significant breakthrough in that they show leptin controls appetite by working with the reward areas in the brain that make food pleasurable.", said Michael Schwartz, an endocrinologist at the University of Washington, Seattle.