The melanocortin-3 receptor is required for entrainment to meal intake

Gregory M. Sutton, Diego Perez-Tilve, Ruben Nogueiras, Jidong Fang, Jason K. Kim, Roger D. Cone, Jeffrey M. Gimble, Matthias H. Tschöp, Andrew A. Butler

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Entrainment of anticipatory activity and wakefulness to nutrient availability is a poorly understood component of energy homeostasis. Restricted feeding (RF) paradigms with a periodicity of 24 h rapidly induce entrainment of rhythms anticipating food presentation that are independent of master clocks in the suprachiasmatic nucleus (SCN) but do require other hypothalamic structures. Here, we report that the melanocortin system, which resides in hypothalamic structures required for food entrainment, is required for expression of food entrainable rhythms. Food anticipatory activity was assessed in wild-type (WT) and melanocortin-3 receptor-deficient (Mc3r-/-) C57BL/J mice by wheel running, spontaneous locomotory movement, and measurement of wakefulness. WT mice housed in wheel cages subject to RF exhibited increased wheel activity during the 2 h preceding meal presentation, which corresponded with an increase in wakefulness around meal time and reduced wakefulness during the dark. WT mice also exhibited increased x- and z-movements centered around food initiation. The activity-based responses to RF were significantly impaired in mice lacking Mc3r. RF also failed to increase wakefulness in the 2 h before food presentation in Mc3r-/- mice. Food entrainment requires expression of Neuronal PAS domain 2 (Npas2) and Period2 (Per2) genes, components of the transcriptional machinery maintaining a clock rhythm. Analysis of cortical gene expression revealed severe abnormalities in rhythmic expression of clock genes (Bmal1, Npas2, Per2) under ad libitum and RF conditions. In summary, Mc3r are required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for normal regulation of cortical clock function.

Original languageEnglish (US)
Pages (from-to)12946-12955
Number of pages10
JournalJournal of Neuroscience
Volume28
Issue number48
DOIs
StatePublished - Nov 26 2008

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Receptor, Melanocortin, Type 3
Meals
Wakefulness
Food
Melanocortins
Gene Components
Gene Expression
Suprachiasmatic Nucleus
Periodicity
Inbred C57BL Mouse
Running
Homeostasis

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Sutton, G. M., Perez-Tilve, D., Nogueiras, R., Fang, J., Kim, J. K., Cone, R. D., ... Butler, A. A. (2008). The melanocortin-3 receptor is required for entrainment to meal intake. Journal of Neuroscience, 28(48), 12946-12955. https://doi.org/10.1523/JNEUROSCI.3615-08.2008
Sutton, Gregory M. ; Perez-Tilve, Diego ; Nogueiras, Ruben ; Fang, Jidong ; Kim, Jason K. ; Cone, Roger D. ; Gimble, Jeffrey M. ; Tschöp, Matthias H. ; Butler, Andrew A. / The melanocortin-3 receptor is required for entrainment to meal intake. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 48. pp. 12946-12955.
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Sutton, GM, Perez-Tilve, D, Nogueiras, R, Fang, J, Kim, JK, Cone, RD, Gimble, JM, Tschöp, MH & Butler, AA 2008, 'The melanocortin-3 receptor is required for entrainment to meal intake', Journal of Neuroscience, vol. 28, no. 48, pp. 12946-12955. https://doi.org/10.1523/JNEUROSCI.3615-08.2008

The melanocortin-3 receptor is required for entrainment to meal intake. / Sutton, Gregory M.; Perez-Tilve, Diego; Nogueiras, Ruben; Fang, Jidong; Kim, Jason K.; Cone, Roger D.; Gimble, Jeffrey M.; Tschöp, Matthias H.; Butler, Andrew A.

In: Journal of Neuroscience, Vol. 28, No. 48, 26.11.2008, p. 12946-12955.

Research output: Contribution to journalArticle

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T1 - The melanocortin-3 receptor is required for entrainment to meal intake

AU - Sutton, Gregory M.

AU - Perez-Tilve, Diego

AU - Nogueiras, Ruben

AU - Fang, Jidong

AU - Kim, Jason K.

AU - Cone, Roger D.

AU - Gimble, Jeffrey M.

AU - Tschöp, Matthias H.

AU - Butler, Andrew A.

PY - 2008/11/26

Y1 - 2008/11/26

N2 - Entrainment of anticipatory activity and wakefulness to nutrient availability is a poorly understood component of energy homeostasis. Restricted feeding (RF) paradigms with a periodicity of 24 h rapidly induce entrainment of rhythms anticipating food presentation that are independent of master clocks in the suprachiasmatic nucleus (SCN) but do require other hypothalamic structures. Here, we report that the melanocortin system, which resides in hypothalamic structures required for food entrainment, is required for expression of food entrainable rhythms. Food anticipatory activity was assessed in wild-type (WT) and melanocortin-3 receptor-deficient (Mc3r-/-) C57BL/J mice by wheel running, spontaneous locomotory movement, and measurement of wakefulness. WT mice housed in wheel cages subject to RF exhibited increased wheel activity during the 2 h preceding meal presentation, which corresponded with an increase in wakefulness around meal time and reduced wakefulness during the dark. WT mice also exhibited increased x- and z-movements centered around food initiation. The activity-based responses to RF were significantly impaired in mice lacking Mc3r. RF also failed to increase wakefulness in the 2 h before food presentation in Mc3r-/- mice. Food entrainment requires expression of Neuronal PAS domain 2 (Npas2) and Period2 (Per2) genes, components of the transcriptional machinery maintaining a clock rhythm. Analysis of cortical gene expression revealed severe abnormalities in rhythmic expression of clock genes (Bmal1, Npas2, Per2) under ad libitum and RF conditions. In summary, Mc3r are required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for normal regulation of cortical clock function.

AB - Entrainment of anticipatory activity and wakefulness to nutrient availability is a poorly understood component of energy homeostasis. Restricted feeding (RF) paradigms with a periodicity of 24 h rapidly induce entrainment of rhythms anticipating food presentation that are independent of master clocks in the suprachiasmatic nucleus (SCN) but do require other hypothalamic structures. Here, we report that the melanocortin system, which resides in hypothalamic structures required for food entrainment, is required for expression of food entrainable rhythms. Food anticipatory activity was assessed in wild-type (WT) and melanocortin-3 receptor-deficient (Mc3r-/-) C57BL/J mice by wheel running, spontaneous locomotory movement, and measurement of wakefulness. WT mice housed in wheel cages subject to RF exhibited increased wheel activity during the 2 h preceding meal presentation, which corresponded with an increase in wakefulness around meal time and reduced wakefulness during the dark. WT mice also exhibited increased x- and z-movements centered around food initiation. The activity-based responses to RF were significantly impaired in mice lacking Mc3r. RF also failed to increase wakefulness in the 2 h before food presentation in Mc3r-/- mice. Food entrainment requires expression of Neuronal PAS domain 2 (Npas2) and Period2 (Per2) genes, components of the transcriptional machinery maintaining a clock rhythm. Analysis of cortical gene expression revealed severe abnormalities in rhythmic expression of clock genes (Bmal1, Npas2, Per2) under ad libitum and RF conditions. In summary, Mc3r are required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for normal regulation of cortical clock function.

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Sutton GM, Perez-Tilve D, Nogueiras R, Fang J, Kim JK, Cone RD et al. The melanocortin-3 receptor is required for entrainment to meal intake. Journal of Neuroscience. 2008 Nov 26;28(48):12946-12955. https://doi.org/10.1523/JNEUROSCI.3615-08.2008