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

Authors :
Xu Y
Jones JE
Kohno D
Williams KW
Lee CE
Choi MJ
Anderson JG
Heisler LK
Zigman JM
Lowell BB
Elmquist JK
Source :
Neuron [Neuron] 2008 Nov 26; Vol. 60 (4), pp. 582-9.
Publication Year :
2008

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.

Details

Language :
English
ISSN :
1097-4199
Volume :
60
Issue :
4
Database :
MEDLINE
Journal :
Neuron
Publication Type :
Academic Journal
Accession number :
19038216
Full Text :
https://doi.org/10.1016/j.neuron.2008.09.033