OHSU scientists locate, characterize key hormone involved in appetite control

Increasing hormone causes increase of appetite, eating

Researchers at Oregon Health & Science University (OHSU) have identified a key hormone involved in appetite control and demonstrated its effect on the brain. Scientists have shown that the hormone, called ghrelin, activates specialized neurons in the hypothalamus involved in weight regulation. The research involved scientists at several collaborating institutions, including: Yale Medical School, Baylor College of Medicine, the University of Alberta and Lilly Research Laboratories. The results are printed in the Feb. 20 edition of the journal Neuron.

Researchers believe this information could be used to develop drugs aimed at stimulating appetite in patients who have undergone extreme weight loss due to illness, a condition known as cachexia. These pharmaceuticals could also assist children who are developing at a slower than normal rate. Conversely, drugs aimed at limiting production of the hormone might be developed to reduce appetite for those battling severe obesity.

“Ghrelin is a hormone produced in the stomach with the ability to stimulate feeding when introduced to specialized weight regulation brain cells called neuropeptide Y neurons. In fact, past research has shown that when ghrelin levels are increased in mice for an extended period, the mice gain weight,” said Michael Cowley, Ph.D., an assistant scientist in the Division of Neuroscience at the OHSU Oregon National Primate Research Center and lead author of the study. “In both mice and humans, ghrelin levels increase naturally in response to weight loss or reduced caloric intake. As expected, the hormone diminishes in response to food intake. In other words, it’s believed to be part of the body’s natural signaling system which informs the brain when it’s time to eat.”

To pinpoint and witness the effects of ghrelin in the brain, the scientists used a method pioneered by OHSU researchers Cowley, Roger Cone, Ph.D., and Malcolm Low, M.D., Ph.D. The researchers used a fluorescent protein to highlight certain neurons, making the brain cells distinguishable from other surrounding neurons. They then used tiny electrodes to record cell activity in response to ghrelin.

“It is remarkable how such a relatively small group of interconnected neurons deep in the brain coordinate the daily signals of hunger and satiety with the body’s long-term energy stores to normally maintain a constant body weight,” said Low, a scientist in the Vollum Institute at OHSU.

The research team also located a new source for ghrelin production in the body. The site is located in a section of the hypothalamus that had no previously known function and that is near the brain region affected by the hormone.

“This research shows that there are two sites where increased appetite may be generated, the stomach and the brain,” explained Cone, a senior scientist at the OHSU Vollum Institute. “We hope future research will hopefully distinguish between the roles of these two production sites so that we may better understand weight regulation and energy homeostasis in the body.”

These latest findings follow a study published in August 2002 that identified and characterized peripheral hormone peptide YY (PYY). PYY appears to have the opposite effect as ghrelin – reducing appetite instead of increasing it. OHSU researchers and their collaborators found that by introducing PYY into the bloodstreams of both humans and mice, a temporary, but measurable drop in appetite and food ingestion occurred.

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This research was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Research Resources, both components of the National Institutes of Health.