5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis.

 

5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis.

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Title: 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis.
Author: Xu, Yong; Jones, Juli E; Kohno, Daisuke; Williams, Kevin W; Lee, Charlotte E; Choi, Michelle J; Anderson, Jason G; Heisler, Lora K; Zigman, Jeffrey M; Lowell, Bradford B; Elmquist, Joel K
Abstract: 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.
Citation: Neuron. 2008 Nov 26 ;60(4): 582-9.
PMC: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19038216

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