5-HT2CRs Expressed by Pro-Opiomelanocortin Neurons Regulate Energy Homeostasis

• DOI: 10.1016/j.neuron.2008.09.033
• Publication Date: 2008-11-27T11:28:40Z
• Authors: Yong Xu; Juli E. Jones; Daisuke Kohno; Kevin W. Williams; Charlotte E. Lee; Michelle J. Choi; Jason G. Anderson; Lora K. Heisler; Jeffrey M. Zigman; Bradford B. Lowell; Joel K. Elmquist
• Keywords: 570; Serotonin; Pro-Opiomelanocortin; 5-HT1C receptor; Neuroscience(all); receptor messenger-RNA; melanocortin system; HUMDISEASE; Drug Resistance; Hypothalamus; 610; Appetite; Hyperphagia; Motor Activity; leptin; MOLNEURO; Mice; 03 medical and health sciences; SDG 3 - Good Health and Well-being; rat-brain; Report; Appetite Depressants; Neural Pathways; body-weight; Receptor, Serotonin, 5-HT2C; Animals; Homeostasis; Obesity; humdisease; Mice, Knockout; 0303 health sciences; Appetite Regulation; nucleus; food-intake; mutant mice; 624; serotonin; molneuro; SIGNALING; RC0321; signaling; Energy Metabolism; RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

Drugs activating 5-hydroxytryptamine 2C receptors (5-HT2CRs) potently suppress appetite, but the underlying mechanisms for these effects are not fully understood. To tackle this issue, we generated mice with global 5-HT2CR deficiency (2C null) and mice with 5-HT2CRs re-expression only in pro-opiomelanocortin (POMC) neurons (2C/POMC mice). We show that 2C null mice predictably developed hyperphagia, hyperactivity, and obesity and showed attenuated responses to anorexigenic 5-HT drugs. Remarkably, all these deficiencies were normalized in 2C/POMC mice. These results demonstrate that 5-HT2CR expression solely in POMC neurons is sufficient to mediate effects of serotoninergic compounds on food intake. The findings also highlight the physiological relevance of the 5-HT2CR-melanocortin circuitry in the long-term regulation of energy balance.