Scientists have new understandings why some weight loss drugs work by enhancing the serotonin levels in the brain.  The diet drugs that have these mood boosting effects on serotonin include sibutramine (marketed as Meridia), and fenfluramine.  Fenfluramine has been recalled because of the combination with dexfenfluramine, marketed as fen-phen because of the possibility of fatal heart valve abnormalities.

How does serotonin suppress appetite?  The group of researchers, led by Michael Cowley of Oregon Health and Science University conducted research on mice to further investigate how serotonin works with the hypothalamus.  They traced the receptors for serotonin and they saw that particular neurons were expressed in this circuitry which directly changed the mice food intake and body weight. They further found a protein called AgRP that stimulated appetite and another protein called áMSH that curbs appetite.  These AgRP protein was reduced when the serotonin and drugs that affected serotonin was present while at the same time the áMSH protein was increased reducing the appetite.

The researchers tested mice to see what effects of the various drugs that enhance or interfere with serotonin would have on their eating behavior.  The drugs helped to disrupt the function of receptors by a substance called melancortin.  Melanocoritin has been known to act for receptors of the proteins AgRP and áMSH which control a person’s appetite. 

Another receptor called melanocortin receptor-4 was identified by the researchers as a critical target of the serotonin pathway, which seems to be the central location for appetite regulation.

The study was first reported in the July 20^th issue in Neuron.  Other researchers that have contributed to this study was Joel Elmquist of University of Texas Southwestern Medical Center at Dallas and formerly of Beth Israel Deaconess Medical Center and Harvard Medical School, and Lora K. Heisler of the University of Cambridge and formerly of Beth Israel Deaconess Medical Center and Harvard Medical School.
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