Yale Researchers Find New Target in the Brain to Regulate Appetite and Food

Ghrelin, a peptide originally found to be produced by the stomach and which induces growth hormone release, appetite and food intake, is also expressed in the hypothalamic appetite center of the brain, according to a Yale researcher.

“Ghrelin-producing cells are distributed in the hypothalamus in a manner that they are in a perfect position to coordinate the activity of the different hypothalamic sub-nuclei already known to regulate daily energy balance,” said Tamas Horvath, senior author of the article in the current issue of the journal Neuron and associate professor of neurobiology and of obstetrics and gynecology at Yale School of Medicine.

In collaboration with other researchers, Horvath and his team also found that this central ghrelin system triggers appropriate electrophysiological responses of other key hypothalamic peptidergic systems.

It had already been proposed that ghrelin was a key peripheral signal informing the brain appetite center about negative energy balance. The mapping of this circuit in the current study offers a new target to regulate appetite and food intake from within the brain, Horvath said.

He also said that the position of this novel set of cells raises the possibility that hypothalamic ghrelin neurons convey messages to the appetite center from sources other than the periphery.

“We believe that these neurons are conveying information regarding circadian rhythm and sensory cues as well,” Horvath said. “You could watch 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.”

He said one hypothesis is that the basic system that carefully regulates food intake and energy expenditure to maintain a constant body weight and fat stores may be suppressed by events such as stress or pregnancy, allowing the neuronal system in the hypothalamus that signals olfactory and visual food cues to dominate.

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

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