From the stomach to the brain: how a peptide hormone sparks appetite

In recent years neurobiologists have taken a keen interest in a peptide hormone called ghrelin. The molecule appears to be involved in activities such as growth hormone release, energy homeostasis and the functioning of the cardiovascular system. Big Pharma sees in it a potential target for diet drugs because of its role in sparking an appetite.

It is also of interest because, although it is produced by the stomach, it is found in the hypothalamus as well. Now researchers at Yale have tracked ghrelin to a group of previously uncharacterized neurons in the brain’s appetite center.

“Ghrelin-producing cells are distributed in the hypothalamus in such a manner that they are in a perfect position to coordinate the activity of the different hypothalamic subnuclei already known to regulate daily energy balance,” said Tamas Horvath, Ph.D., D.V.M. senior author of an article in the February 20 issue of Neuron and associate professor of obstetrics and gynecology and neurobiology.

Studies in rats and humans had already shown that ghrelin signals the brain’s appetite center when energy levels are low. Levels of ghrelin rose before and declined after meals. The mapping of the ghrelin circuit to neurons in the brain offers a new target for regulating appetite and food intake, Horvath said.

“We believe that these neurons are conveying information regarding circadian rhythm and sensory clues as well,” he said. “You could be watching a movie, see food and become hungry, or be in the kitchen and smell something and become hungry, even if your stomach is full. These brain ghrelin neurons may be those that enable these brain processes to dominate over the actual need for energy intake.”

One hypothesis, Horvath said, is that the system that balances food consumption, energy expenditure, body weight and fat stores may be suppressed by events such as stress or pregnancy. The neuronal system that signals olfactory and visual clues would then dominate.

“We are now working to find out how ghrelin from the stomach and from the brain work together or independently to regulate appetite or food intake and other brain mechanisms,” Horvath said.