The research team stated that this discovery may open the way to the development of new, effective weight-control medications.
Research with mice has shown how diet
medications, such as Fen-Phen, work to activate a chemical
substance in the brain called serotonin, which controls appetite.
The researchers said that this finding could lead to new
weight-control medications that don't have the dangerous cardiac
side effects associated with Fen-Phen, which led it to be banned in
1997, after it had been used for almost a decade.
"We wanted to study the pathways and molecules related to the anorexic (appetite-suppressant) properties of drugs like Fen-Phen," stated the lead researcher Dr. Joel Elmquist, a professor of internal medicine at the University of Texas Southwestern Medical Center at Dallas, and director of the Center for Hypothalamic Research.
Elmquist emphasized that what was more noticeable about Fen-Phen was that it didsuppress appetite and result in weight loss. "But the mechanism and the brain pathways that were responsible for such actions were basically unknown," he explained. In this study, Elmquist and his colleagues tested the effects of several medications that alter the brain’s serotonin levels in mice. They found that serotonin activates some neurons and melanocortin-4 receptors—known as MC4Rs—to control appetite, and at the same time it blocks other neurons that normally increase appetite. The report was published in the July 20 issue of Neuron.
"These results suggest that the melanocortin pathway is a key pathway in your brain that affects food intake, body weight and glucose," Elmquist stated. "Our data suggest that serotonin is involved with this pathway." This dual effect helps to explain how these drugs cause weight loss. The findings also reinforce the role of serotonin—which regulates emotions, mood, and sleep—in affecting the melanocortin system in the brain, a key pathway that controls body weight, he explained.
Learning how these drugs work, we could potentially target those pathways and avoid the harmful side effects associated with a medication like Fen-Phen, while still controlling hunger, Elmquist said. "The goal of pharmaceutical laboratories is to identify the neurons that are key to body-weight control and, within those neurons, the key signaling pathways," Elmquist added. "If we could target them, we could have a much more effective and safe treatment," he stated.
One expert agrees that it may be possible to develop new, safe, and effective weight-control medications, but only to be used as a “bridge” to ultimate changes in lifestyle. Phillip Smith, director of the Division of Diabetes, Endocrinology and Metabolic Diseases at the National Institute of Diabetes, Digestive and Kidney Diseases said: "This finding really shows us where we can focus our efforts for new therapeutic agents that target the receptor they have identified as key in the regulation of food intake."
Smith thinks that these new medications could target centers of the brain that control behavior. "The key is what promotes behaviors like overeating and smoking," he assured. "Medications that target the pathways found in this study are likely to affect motivational pathways involved with serotonin."
But medications alone are not the answer to the growing obesity epidemic, Smith said. "The only hope is to modify lifestyle," he emphasized.
"The question is: can we find medications that will help us do that? Not a lifetime drug. Perhaps like a nicotine patch, one could imagine a patch that would help you in the hardest part of losing weight so that you could actually change your lifestyle, without constantly fighting the desire to eat," Smith said. "It is an ultimate lifestyle change that will really make a difference in the obesity epidemic.
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