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

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.

Pubmed ID: 19038216


  • Xu Y
  • Jones JE
  • Kohno D
  • Williams KW
  • Lee CE
  • Choi MJ
  • Anderson JG
  • Heisler LK
  • Zigman JM
  • Lowell BB
  • Elmquist JK



Publication Data

November 26, 2008

Associated Grants

  • Agency: Wellcome Trust, Id: 081713
  • Agency: NIDDK NIH HHS, Id: DK065171
  • Agency: NIDDK NIH HHS, Id: F32 DK63853-01
  • Agency: NIDDK NIH HHS, Id: K08DK068069-01A2
  • Agency: NIDDK NIH HHS, Id: P01 DK56116
  • Agency: NIDDK NIH HHS, Id: R00 DK085330
  • Agency: NIDDK NIH HHS, Id: R01 DK053301
  • Agency: NIMH NIH HHS, Id: R01 MH061583
  • Agency: NIDDK NIH HHS, Id: R01DK53301
  • Agency: NIMH NIH HHS, Id: R01MH61583
  • Agency: NIDDK NIH HHS, Id: RL1 DK081185
  • Agency: NIDDK NIH HHS, Id: RL1DK081185
  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Animals
  • Appetite
  • Appetite Depressants
  • Appetite Regulation
  • Drug Resistance
  • Energy Metabolism
  • Homeostasis
  • Hyperphagia
  • Hypothalamus
  • Mice
  • Mice, Knockout
  • Motor Activity
  • Neural Pathways
  • Obesity
  • Pro-Opiomelanocortin
  • Receptor, Serotonin, 5-HT2C
  • Serotonin