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

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*

*Corresponding author for this work

Research output: Contribution to journalArticle

194 Citations (Scopus)
7 Downloads (Pure)

Abstract

Drugs activating 5-hydroxytryptamine 2C receptors (5-HT(2C)Rs) potently suppress appetite, but the underlying mechanisms for these effects are not fully understood. To tackle this issue, we generated mice with global 5-HT(2C)R deficiency (2C null) and mice with 5-HT(2C)Rs 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-HT(2C)R 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-HT(2C)R-melanocortin circuitry in the long-term regulation of energy balance.

Original languageEnglish
Pages (from-to)582-589
Number of pages8
JournalNeuron
Volume60
Issue number4
DOIs
Publication statusPublished - 25 Nov 2008

Keywords

  • receptor messenger-RNA
  • food-intake
  • melanocortin system
  • 5-HT1C receptor
  • mutant mice
  • body-weight
  • rat-brain
  • serotonin
  • leptin
  • nucleus

Cite this

Xu, Y., Jones, J. E., Kohno, D., Williams, K. W., Lee, C. E., Choi, M. J., Anderson, J. G., Heisler, L. K., Zigman, J. M., Lowell, B. B., & Elmquist, J. K. (2008). 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis. Neuron, 60(4), 582-589. https://doi.org/10.1016/j.neuron.2008.09.033