Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake

Lora K. Heisler; Erin E. Jobst; Gregory M. Sutton; Ligang Zhou; Erzsebet Borok; Zoe Thornton-Jones; Hong Yan Liu; Jeffrey M. Zigman; Nina Balthasar; Toshiro Kishi; Charlotte E. Lee; Carl J. Aschkenasi; Chen Yu Zhang; Jia Yu; Olivier Boss; Kathleen G. Mountjoy; Peter G. Clifton; Bradford B. Lowell; Jeffrey M. Friedman; Tamas Horvath; Andrew A. Butler; Joel K. Elmquist; Michael A. Cowley

doi:10.1016/j.neuron.2006.06.004

Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake

Lora K. Heisler, Erin E. Jobst, Gregory M. Sutton, Ligang Zhou, Erzsebet Borok, Zoe Thornton-Jones, Hong Yan Liu, Jeffrey M. Zigman, Nina Balthasar, Toshiro Kishi, Charlotte E. Lee, Carl J. Aschkenasi, Chen Yu Zhang, Jia Yu, Olivier Boss, Kathleen G. Mountjoy, Peter G. Clifton, Bradford B. Lowell, Jeffrey M. Friedman, Tamas HorvathAndrew A. Butler, Joel K. Elmquist, Michael A. Cowley

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336 Scopus citations

Abstract

The neural pathways through which central serotonergic systems regulate food intake and body weight remain to be fully elucidated. We report that serotonin, via action at serotonin1B receptors (5-HT_1BRs), modulates the endogenous release of both agonists and antagonists of the melanocortin receptors, which are a core component of the central circuitry controlling body weight homeostasis. We also show that serotonin-induced hypophagia requires downstream activation of melanocortin 4, but not melanocortin 3, receptors. These results identify a primary mechanism underlying the serotonergic regulation of energy balance and provide an example of a centrally derived signal that reciprocally regulates melanocortin receptor agonists and antagonists in a similar manner to peripheral adiposity signals.

Original language	English (US)
Pages (from-to)	239-249
Number of pages	11
Journal	Neuron
Volume	51
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2006.06.004
State	Published - Jul 20 2006

Keywords

HUMDISEASE
MOLNEURO

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2006.06.004

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Heisler, L. K., Jobst, E. E., Sutton, G. M., Zhou, L., Borok, E., Thornton-Jones, Z., Liu, H. Y., Zigman, J. M., Balthasar, N., Kishi, T., Lee, C. E., Aschkenasi, C. J., Zhang, C. Y., Yu, J., Boss, O., Mountjoy, K. G., Clifton, P. G., Lowell, B. B., Friedman, J. M., ... Cowley, M. A. (2006). Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake. Neuron, 51(2), 239-249. https://doi.org/10.1016/j.neuron.2006.06.004

Heisler, LK, Jobst, EE, Sutton, GM, Zhou, L, Borok, E, Thornton-Jones, Z, Liu, HY, Zigman, JM, Balthasar, N, Kishi, T, Lee, CE, Aschkenasi, CJ, Zhang, CY, Yu, J, Boss, O, Mountjoy, KG, Clifton, PG, Lowell, BB, Friedman, JM, Horvath, T, Butler, AA, Elmquist, JK & Cowley, MA 2006, 'Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake', Neuron, vol. 51, no. 2, pp. 239-249. https://doi.org/10.1016/j.neuron.2006.06.004

@article{4703122e30bf4df8ad5cc5d26f479dce,

title = "Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake",

abstract = "The neural pathways through which central serotonergic systems regulate food intake and body weight remain to be fully elucidated. We report that serotonin, via action at serotonin1B receptors (5-HT1BRs), modulates the endogenous release of both agonists and antagonists of the melanocortin receptors, which are a core component of the central circuitry controlling body weight homeostasis. We also show that serotonin-induced hypophagia requires downstream activation of melanocortin 4, but not melanocortin 3, receptors. These results identify a primary mechanism underlying the serotonergic regulation of energy balance and provide an example of a centrally derived signal that reciprocally regulates melanocortin receptor agonists and antagonists in a similar manner to peripheral adiposity signals.",

keywords = "HUMDISEASE, MOLNEURO",

author = "Heisler, {Lora K.} and Jobst, {Erin E.} and Sutton, {Gregory M.} and Ligang Zhou and Erzsebet Borok and Zoe Thornton-Jones and Liu, {Hong Yan} and Zigman, {Jeffrey M.} and Nina Balthasar and Toshiro Kishi and Lee, {Charlotte E.} and Aschkenasi, {Carl J.} and Zhang, {Chen Yu} and Jia Yu and Olivier Boss and Mountjoy, {Kathleen G.} and Clifton, {Peter G.} and Lowell, {Bradford B.} and Friedman, {Jeffrey M.} and Tamas Horvath and Butler, {Andrew A.} and Elmquist, {Joel K.} and Cowley, {Michael A.}",

note = "Funding Information: We would like to thank Julie Oustecky, Ryan White, Vinsee Tang, and Chris Kenny for their invaluable assistance. Data presented in this paper were supported by the following L.K.H. (NIDDK DK065171, American Diabetes Association, and Boston Obesity Nutrition Research Center), N.B. (The Wellcome Trust, UK, ADA-EASD Transatlantic Fellowship, and Boston Obesity Nutrition Research Center), P.G.C. (BBSRC C505291), B.B.L. (NIDDK56116 and DK53301), A.A.B. (NIDDK DK068330 and American Diabetes Association), T.H. (NIDDK DK074386 and DK060711), J.K.E. (NIMH MH061583, NIDDK P01DK056116), and M.A.C. (NIH RR 00163, NIDDK, DK62202). M.A.C. and OHSU have a significant financial interest in Orexigen Therapeutics Inc., a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by the OHSU Conflict of Interest in Research Committee and the Integrity Program Oversight Council.",

year = "2006",

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doi = "10.1016/j.neuron.2006.06.004",

language = "English (US)",

volume = "51",

pages = "239--249",

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T1 - Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake

AU - Heisler, Lora K.

AU - Jobst, Erin E.

AU - Sutton, Gregory M.

AU - Zhou, Ligang

AU - Borok, Erzsebet

AU - Thornton-Jones, Zoe

AU - Liu, Hong Yan

AU - Zigman, Jeffrey M.

AU - Balthasar, Nina

AU - Kishi, Toshiro

AU - Lee, Charlotte E.

AU - Aschkenasi, Carl J.

AU - Zhang, Chen Yu

AU - Yu, Jia

AU - Boss, Olivier

AU - Mountjoy, Kathleen G.

AU - Clifton, Peter G.

AU - Lowell, Bradford B.

AU - Friedman, Jeffrey M.

AU - Horvath, Tamas

AU - Butler, Andrew A.

AU - Elmquist, Joel K.

AU - Cowley, Michael A.

N1 - Funding Information: We would like to thank Julie Oustecky, Ryan White, Vinsee Tang, and Chris Kenny for their invaluable assistance. Data presented in this paper were supported by the following L.K.H. (NIDDK DK065171, American Diabetes Association, and Boston Obesity Nutrition Research Center), N.B. (The Wellcome Trust, UK, ADA-EASD Transatlantic Fellowship, and Boston Obesity Nutrition Research Center), P.G.C. (BBSRC C505291), B.B.L. (NIDDK56116 and DK53301), A.A.B. (NIDDK DK068330 and American Diabetes Association), T.H. (NIDDK DK074386 and DK060711), J.K.E. (NIMH MH061583, NIDDK P01DK056116), and M.A.C. (NIH RR 00163, NIDDK, DK62202). M.A.C. and OHSU have a significant financial interest in Orexigen Therapeutics Inc., a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by the OHSU Conflict of Interest in Research Committee and the Integrity Program Oversight Council.

PY - 2006/7/20

Y1 - 2006/7/20

N2 - The neural pathways through which central serotonergic systems regulate food intake and body weight remain to be fully elucidated. We report that serotonin, via action at serotonin1B receptors (5-HT1BRs), modulates the endogenous release of both agonists and antagonists of the melanocortin receptors, which are a core component of the central circuitry controlling body weight homeostasis. We also show that serotonin-induced hypophagia requires downstream activation of melanocortin 4, but not melanocortin 3, receptors. These results identify a primary mechanism underlying the serotonergic regulation of energy balance and provide an example of a centrally derived signal that reciprocally regulates melanocortin receptor agonists and antagonists in a similar manner to peripheral adiposity signals.

AB - The neural pathways through which central serotonergic systems regulate food intake and body weight remain to be fully elucidated. We report that serotonin, via action at serotonin1B receptors (5-HT1BRs), modulates the endogenous release of both agonists and antagonists of the melanocortin receptors, which are a core component of the central circuitry controlling body weight homeostasis. We also show that serotonin-induced hypophagia requires downstream activation of melanocortin 4, but not melanocortin 3, receptors. These results identify a primary mechanism underlying the serotonergic regulation of energy balance and provide an example of a centrally derived signal that reciprocally regulates melanocortin receptor agonists and antagonists in a similar manner to peripheral adiposity signals.

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AN - SCOPUS:33745978779

SN - 0896-6273

VL - 51

SP - 239

EP - 249

JO - Neuron

JF - Neuron

IS - 2

ER -

Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake

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