[HTML][HTML] 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis

Y Xu, JE Jones, D Kohno, KW Williams, CE Lee… - Neuron, 2008 - cell.com
Y Xu, JE Jones, D Kohno, KW Williams, CE Lee, MJ Choi, JG Anderson, LK Heisler
Neuron, 2008cell.com
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 …
Summary
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.
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