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5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis.
- 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.
- Subjects :
- Animals
Appetite drug effects
Appetite genetics
Appetite Depressants pharmacology
Appetite Regulation genetics
Drug Resistance genetics
Hyperphagia genetics
Hyperphagia metabolism
Hyperphagia physiopathology
Hypothalamus cytology
Mice
Mice, Knockout
Motor Activity genetics
Neural Pathways cytology
Neural Pathways metabolism
Obesity genetics
Obesity metabolism
Obesity physiopathology
Energy Metabolism genetics
Homeostasis genetics
Hypothalamus metabolism
Pro-Opiomelanocortin metabolism
Receptor, Serotonin, 5-HT2C genetics
Serotonin metabolism
Subjects
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