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OHSU Scientists Locate "Fat Thermostat" in Brain

09/23/99   Portland, Ore.

Research Helps Scientists Understand "Thermostat-like" Mechanism in the Brain Believed to Control Appetite, Weight Loss and Weight Gain.

It's the same story for thousands of overweight Americans fighting the battle of the bulge. They diet to lose weight, only to regain those extra pounds once they return to their normal eating habits. Now, thanks in part to the work of researchers at Oregon Health Sciences University, the actual neurons involved in coordinating appetite and metabolism control in the brain may have been identified.

Roger Cone, Ph.D., a senior scientist at the Vollum Institute at OHSU, working in collaboration with William Colmers, Ph.D., at the University of Alberta, has discovered one of the mechanisms in the brain that apparently memorizes and regulates a person's weight. The mechanism located in the hypothalamus has been named the adipostat by researchers due to the fact that it essentially acts as a fat thermostat.

Previous studies have already shown how the brain reacts to a change in diet and why losing weight can be a battle for many. "When you lose weight, the body thinks there's something wrong," said Cone. "The body thinks you're undergoing starvation or disease and it initiates a number of responses to prevent you from losing weight and even to help you put weight back on. These responses include a decrease in the metabolic rate and an increase in muscle efficiency to limit energy loss."

For years, scientists have proposed the existence of an adipostat in the brain. But until now, its mechanism has remained a mystery. Cone and Colmers, aided by an international team of scientists including Michael Cowley, Ph.D., Nina Pronchuk, Ph.D., and Wei Fan, M.D., have identified individual neurons within the hypothalamus with the precise properties of the long-predicted adipostat.

To find the adipostat, researchers traced the routes of two fiber pathways that appear to play a role in feeding and metabolism. Cone compares the process to tracing electrical wires in your home back to the fuse box.

One of the pathways to the adipostat, called the NPY/AGRP, stimulates feeding. The other pathway, called the MSH, inhibits feeding and is involved in the normal maintenance of metabolic rates. Cone and Colmers used miniature electrodes to identify for the first time neurons that could process information from both pathways.

While there is much more to be learned about the body's metabolism controls, this research could lead to medications that can be used to help regulate a patient's weight. For example, a dieting patient might take a drug that resets the body's adipostat to a lower level, making weight loss easier.

"There are a large number of companies working on drugs that stimulate these receptors in the brain because, in theory, they could prevent excessive caloric intake and energy storage," said Cone. "This would allow people to not only lose weight more efficiently, but to keep it off."

Cone and Colmers findings are published in the Sept. 23 edition of the journal Neuron.

Editors: Dr. Cone is available to comment on his work. Please contact Jim Newman in University News and Publications at (503) 494-8231 to set up interviews.

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