Scientists have long known that hunger causes increases in some brain chemicals while lowering others. However, the root cause of hunger's effects -- the initial chemical trigger of appetite -- has been elusive.

In experiments with mice, the Johns Hopkins researchers showed that appetite is immediately and directly tied to amounts of a chemical called malonyl-CoA. In hungry mice, malonyl-CoA was almost undetectable in the brain. Once fasting mice were given food, however, amounts of the chemical increased to high levels within two hours. Furthermore, chemically reducing appetite by injecting a compound called C75 into the brain brought levels of malonyl-CoA up to those of mice given food, helping to explain C75's effects.

"From this work, it appears as though malonyl-CoA levels control appetite and levels of other brain chemicals that we know go up and down with hunger and feeding," says Dan Lane, Ph.D., professor of biological chemistry in Hopkins' Institute for Basic Biomedical Sciences. "There may be other contributors, but this is the first direct evidence that malonyl-CoA could be the body's primary appetite controller."

In previous work, Lane and his colleagues had shown that giving mice C75, which blocks conversion of malonyl-CoA into fatty acids, dramatically reduced animals' appetites. Subsequently, they found that C75 triggers levels of several known appetite signals (NPY, AgRP, POMC and others) to register "full" even when animals should have been hungry.

However, the new experiments, during which C75 was injected directly into the animals' brains, suggest that increasing levels of malonyl-CoA, caused by "blocking the dam" with
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
18-Dec-2003