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

doi:10.1016/j.neuron.2008.09.033

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

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	582-589
Number of pages	8
Journal	Neuron
Volume	60
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2008.09.033
Publication status	Published - 25 Nov 2008

Keywords

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

UN SDGs

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10.1016/j.neuron.2008.09.033

5-HT2CRs Expressed by Pro-Opiomelanocortin Neurons Regulate Energy Homeostasis
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title = "5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis",

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.",

keywords = "receptor messenger-RNA, food-intake, melanocortin system, 5-HT1C receptor, mutant mice, body-weight, rat-brain, serotonin, leptin, nucleus",

author = "Yong Xu and Jones, {Juli E.} and Daisuke Kohno and Williams, {Kevin W.} and Lee, {Charlotte E.} and Choi, {Michelle J.} and Anderson, {Jason G.} and Heisler, {Lora K.} and Zigman, {Jeffrey M.} and Lowell, {Bradford B.} and Elmquist, {Joel K.}",

note = "Open Access funded by Wellcome",

year = "2008",

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day = "25",

doi = "10.1016/j.neuron.2008.09.033",

language = "English",

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T1 - 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis

AU - Xu, Yong

AU - Jones, Juli E.

AU - Kohno, Daisuke

AU - Williams, Kevin W.

AU - Lee, Charlotte E.

AU - Choi, Michelle J.

AU - Anderson, Jason G.

AU - Heisler, Lora K.

AU - Zigman, Jeffrey M.

AU - Lowell, Bradford B.

AU - Elmquist, Joel K.

N1 - Open Access funded by Wellcome

PY - 2008/11/25

Y1 - 2008/11/25

N2 - 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.

AB - 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.

KW - receptor messenger-RNA

KW - food-intake

KW - melanocortin system

KW - 5-HT1C receptor

KW - mutant mice

KW - body-weight

KW - rat-brain

KW - serotonin

KW - leptin

KW - nucleus

U2 - 10.1016/j.neuron.2008.09.033

DO - 10.1016/j.neuron.2008.09.033

M3 - Article

VL - 60

SP - 582

EP - 589

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

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