Genetic mouse models have provided surprising insight into mechanisms linking serotoninergic compounds with the regulation of feeding behavior and body weight.
The research, published by Cell Press in the November 26th issue of the journal Neuron , pinpoints a specific group of brain cells that mediate energy balance and may lead to the development of antiobesity drugs with fewer side effects.
The 5-hydroxytryptamine (5-HT) system, which includes the 5-HT2C receptor (5-HT2CR) subtype, has been shown to play an important role in the regulation of energy homeostasis. Previous work demonstrated that excessive food intake and obesity are linked with 5-HT2CR deficiency and that the atypical antipsychotic drugs, which appear to block 5-HT2CRs, are associated with serious weight gain. Further, 5-HT2CRs are known to contribute to the appetite suppressant effects of d-fenfluramine, a drug widely prescribed to combat obesity in the 1990s that was later banned because of a negative impact on the heart.
"We have known for some time that drugs activating 5-HT2CRs potently suppress appetite, but the underlying mechanisms for these effects are not fully understood," says senior study author Dr. Joel K. Elmquist from the University of Texas Southwestern Medical Center at Dallas. "We also know that pro-opiomelanocortin (POMC) neurons in the hypothalamus of the brain release neuropeptides that activate the central melanocortin receptors which is required to maintain food intake, body weight and glucose homeostasis. The melanocortin pathway has been hypothesized to be a downstream mediator of the effects of 5-HT2CRs on feeding behavior."