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Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system

Nature Neuroscience volume 7, pages 335–336 (2004)Cite this article

Abstract

Hypothalamic pro-opiomelanocortin (POMC) neurons help regulate long-term energy stores. POMC neurons are also found in the nucleus tractus solitarius (NTS), a region regulating satiety. We show here that mouse brainstem NTS POMC neurons are activated by cholecystokinin (CCK) and feeding-induced satiety and that activation of the neuronal melanocortin-4 receptor (MC4-R) is required for CCK-induced suppression of feeding; the melanocortin system thus provides a potential substrate for integration of long-term adipostatic and short-term satiety signals.

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Figure 1: CCK-8s activates POMC neurons in the NTS.
Figure 2: Brainstem MC4-R signaling is required for CCK-8s-induced feeding inhibition.

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Acknowledgements

Supported by US National Institutes of Health grants DK55819 (R.D.C.) and DK62179 (W.F.), and a grant from the Wellcome Trust (K.L.J.E.). POMC-EGFP mice were a kind gift of M. Low (Oregon Health and Science University).

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Authors and Affiliations

  1. Vollum Institute, Oregon Health and Science University, Portland, 97239-3098, Oregon, USA

    Wei Fan, Kate L J Ellacott, Ilia G Halatchev, Kanji Takahashi, Pinxuan Yu & Roger D Cone

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  1. Wei Fan
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  2. Kate L J Ellacott
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  3. Ilia G Halatchev
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  4. Kanji Takahashi
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  5. Pinxuan Yu
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  6. Roger D Cone
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Correspondence to Wei Fan or Roger D Cone.

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Competing interests

R.D.C. and Oregon Health and Science University have a significant financial interest in Neurocrine Biosciences, 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.

Supplementary information

Supplementary Fig. 1

Feeding activates NTS POMC neurons. (a) c-Fos-IR neurons in the NTS 60 minutes after food intake (b) POMC-EGFP-IR cells in the NTS 60 minutes after food intake. (c) Colocalization of c-Fos and POMC in NTS neurons 60 minutes after food intake. (d) The percent of NTS POMC neurons at 1100h expressing c-Fos in ARC and NTS in control (fasted) animals, or animals receiving food (fed) at 9000-1000h. (e) Percent of c-Fos-IR neurons in ARC or NTS expressing POMC-EGFP in animals in the fed (n=8) or fasted state (n=3). ***P<0.001. Size bar (a) = 100μM. Arrows indicate cells expressing both EGFP-IR and c-Fos-IR. (JPG 38 kb)

Supplementary Fig. 2

POMC expression defines a unique population of TH-negative, GLP-1-negative cells within the NTS. (a) Anti-tyrosine hydroxylase (TH) antibodies identify distinct TH-positive neurons (red) within in the same region of the NTS as POMC-EGFP-IR neurons. (b) Anti-EGFP antibodies are used to detect POMC neurons (green) in the NTS of the EGFP-POMC mouse. (c) No coexpression of POMC and TH expression was observed in individual neurons of the mouse NTS. (d,e) POMC-EGFP-IR cells were generally found medial of GLP-1-IR cells in the NTS. No co-expression of the peptides was observed. Size bars indicate 135 μM (a-c), 250 μM (d), and 50 μM (e). CC, central canal; AP, area postrema. (JPG 42 kb)

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Fan, W., Ellacott, K., Halatchev, I. et al. Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Nat Neurosci 7, 335–336 (2004). https://doi.org/10.1038/nn1214

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