No matter how much Homer Simpson eats, the lovable cartoon character still salivates at the mere sight of food. Homer's animated brain might be lacking a hormone called leptin, if one accepts a new study indicating that the protein is a key player in control of food cravings. The research, published online yesterday in Science, has wider implications for understanding the way the brain regulates appetite and, ultimately, the causes of obesity.
Leptin is already known to be a key player in appetite, acting as a sensor for the body's energy storage (ScienceNOW, 1 November 2001). Fat tissue releases leptin into the bloodstream, signaling the brain that the body has had enough to eat. When fat stores become depleted, leptin levels fall and the brain stimulates hunger. But researchers have been unclear whether the hormone affects the higher brain areas that mediate feelings of craving and reward. Endocrinologist Sadaf Farooqi of the University of Cambridge, U.K., and her colleagues addressed question this by studying a 14-year-old boy and a 19-year-old girl unable to produce leptin.
Using functional magnetic resonance imaging (fMRI), the researchers scanned the brain activity of the volunteers in their natural (leptin-deficient) condition, once in a fasted state and again after eating. During each scan, the subjects were shown pictures of food and nonfood control images. The volunteers showed greater activation in reward-related brain areas in response to the food images, regardless of whether they had eaten, and they consistently rated the food images as highly desirable. The volunteers were then treated with leptin for 7 days, and the fMRI scans were repeated in fed and fasted states. This time, the volunteers only showed the greater brain activation with food images if they had been fasting, and on average they rated the food images as less desirable if they had eaten.
The researchers conclude that leptin plays an important role in the brain's ability to tell the difference between the fed and fasted states. Before their leptin-replacement treatments, the volunteers permanently felt like hungry diners watching others being served first.
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, says Jeffrey Friedman, a geneticist at Rockefeller University in New York who originally identified the role of leptin in appetite. Michael Schwartz, an endocrinologist at the University of Washington, Seattle, agrees that 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.