Experimental appetite suppressant affects numerous brain messengers in mice

Johns Hopkins scientists report success in figuring out how an experimental compound prevents mice from recognizing that it's time to eat, profoundly suppressing appetite and causing weight loss.

The compound, called C75, alters the natural balance of brain messengers that normally send signals of hunger during fasting and of satiety when full. In both lean and obese mice, C75 affects those signals, according to a report on the work in the Dec. 26 online version of the Proceedings of the National Academy of Sciences.

Obesity in humans is a major public health problem and is linked to a heightened risk of developing diabetes, stroke and heart disease. While mice are not men, there are common pathways in fundamental activities.

"If we can understand the pathway that triggers eating, we may be able to find safe ways to intervene," says Daniel Lane, Ph.D., professor of biological chemistry in the School of Medicine's Institute for Basic Biomedical Sciences. "We're close to figuring out how these neurotransmitters are connected, at least in mice, and what really affects their expression."

Building on the knowledge that C75 blocks the enzyme fatty acid synthase, which helps the body store energy, Lane and others last year reported that mice given C75 stopped eating and lost about 5 percent of their body weight in just a day.

In the new study of lean (normal) mice and mice genetically engineered to be obese, the scientists looked for changes in the appetite signals in animals that fasted for one day and those injected with C75. While neither group ate, mice injected with C75 had more of the "satisfied" signals and less of the "hungry" signals than other mice.

Normally, fasting dramatically increases the amounts of two neurotransmitters, AgRP and NPY. Coming from neurons in a particular area of the hypothalamus, a small structure inside the brain, these messengers tell the animal to eat. When f

Contact: Joanna Downer
Johns Hopkins Medical Institutions

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