Appetite surpressant sends the right signals
stage. Scientists in the United States claim this week that a
compound, called C75, successfully alters the natural balance of
brain messengers that normally send signals of hunger during
fasting and of satiety when full.
Research into a new appetite suppressant may have reached a new stage. Scientists in the United States claim this week that a compound, called C75, successfully alters the natural balance of brain messengers that normally send signals of hunger during fasting and of satiety when full.
According to a report on the work in the Dec. 26 online version of the Proceedings of the National Academy of Sciences researchers at the John Hopkins Medical Institution found that in both lean and obese mice, C75 affects those signals.
"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."
The scientists write that 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 fasting animals are given food, they'll eat immediately, says Lane.
In both lean and obese mice treated with C75, however, levels of these two messengers did not increase, instead staying close to the levels of mice allowed to eat at will. The C75 mice ignored food, even though they had access to it, continued Lane.
"Essentially, animals given C75 don't recognize that they are not eating,"said Lane. "The levels of neurotransmitters that stimulate appetite and those that inhibit appetite are in line with what they would be if the mouse were eating normally."
The scientists are still trying to understand exactly how C75 has these effects. C75 blocks fatty acid synthase, but isn't directly involved in the production of any of these neurotransmitters, says Lane. Their working hypothesis is that a molecule called malonyl CoA is the real trigger for these changes in neurotransmitter levels. Malonyl CoA is normally transformed into a fatty acid by fatty acid synthase. When C75 blocks fatty acid synthase, levels of malonyl CoA rise.
Lane says the hypothalamus may recognize increased levels of malonyl CoA as a signal that the animal is eating enough, and thus the molecule may be directly involved in regulating appetite-related messengers. Malonyl CoA is already known as a regulator in some energy-burning processes.
"Our experiments show that NPY and AgRP are blocked at the signal of gene expression by C75 treatment," commented Teruhiko Shimokawa, Ph.D., a visiting scientist, working with Lane, from Yamanouchi Pharmaceutical Co. in Tokyo. "In this story, the malonyl CoA hypothesis is very attractive and very promising."
Shimokawa, who developed a technique to measure RNA of the neurotransmitters, notes that obesity is a growing problem in Japan as lifestyles have become more Westernized since World War II. "Obesity is a very serious situation," he said.
According to a statement the scientists will continue to study C75 and to investigate whether malonyl CoA is the real trigger.
