The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis

Michael A. Cowley, Roy G. Smith, Sabrina Diano, Matthias Tschöp, Nina Pronchuk, Kevin L. Grove, Christian J. Strasburger, Martin Bidlingmaier, Michael Esterman, Mark L. Heiman, Luis Miguel Garcia-Segura, Eduardo A. Nillni, Pablo Mendez, Malcolm J. Low, P. Sótonyi, Jeffrey M. Friedman, Hongyan Liu, Shirly Pinto, William F. Colmers, Roger D. Cone & 1 others Tamas L. Horvath

Research output: Contribution to journalArticle

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Abstract

The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing neuropeptide Y (NPY), Agouti-related protein (AGRP), proopiomelanocortin (POMC) products, and corticotropin-releasing hormone (CRH). Within the hypothalamus, ghrelin bound mostly on presynaptic terminals of NPY neurons. Using electrophysiological recordings, we found that ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH). We propose that at these sites, release of ghrelin may stimulate the release of orexigenic peptides and neurotransmitters, thus representing a novel regulatory circuit controlling energy homeostasis.

Original languageEnglish
Pages (from-to)649-661
Number of pages13
JournalNeuron
Volume37
Issue number4
DOIs
Publication statusPublished - Feb 20 2003

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Ghrelin
Neuropeptide Y
Homeostasis
Paraventricular Hypothalamic Nucleus
Neurons
Hypothalamus
Agouti-Related Protein
Efferent Neurons
Gastrointestinal Hormones
Pro-Opiomelanocortin
Arcuate Nucleus of Hypothalamus
Third Ventricle
Peptide Hormones
Corticotropin-Releasing Hormone
Presynaptic Terminals
Appetite
Neurotransmitter Agents
Rodentia
Peptides

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cowley, M. A., Smith, R. G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K. L., ... Horvath, T. L. (2003). The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron, 37(4), 649-661. https://doi.org/10.1016/S0896-6273(03)00063-1

The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. / Cowley, Michael A.; Smith, Roy G.; Diano, Sabrina; Tschöp, Matthias; Pronchuk, Nina; Grove, Kevin L.; Strasburger, Christian J.; Bidlingmaier, Martin; Esterman, Michael; Heiman, Mark L.; Garcia-Segura, Luis Miguel; Nillni, Eduardo A.; Mendez, Pablo; Low, Malcolm J.; Sótonyi, P.; Friedman, Jeffrey M.; Liu, Hongyan; Pinto, Shirly; Colmers, William F.; Cone, Roger D.; Horvath, Tamas L.

In: Neuron, Vol. 37, No. 4, 20.02.2003, p. 649-661.

Research output: Contribution to journalArticle

Cowley, MA, Smith, RG, Diano, S, Tschöp, M, Pronchuk, N, Grove, KL, Strasburger, CJ, Bidlingmaier, M, Esterman, M, Heiman, ML, Garcia-Segura, LM, Nillni, EA, Mendez, P, Low, MJ, Sótonyi, P, Friedman, JM, Liu, H, Pinto, S, Colmers, WF, Cone, RD & Horvath, TL 2003, 'The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis', Neuron, vol. 37, no. 4, pp. 649-661. https://doi.org/10.1016/S0896-6273(03)00063-1
Cowley, Michael A. ; Smith, Roy G. ; Diano, Sabrina ; Tschöp, Matthias ; Pronchuk, Nina ; Grove, Kevin L. ; Strasburger, Christian J. ; Bidlingmaier, Martin ; Esterman, Michael ; Heiman, Mark L. ; Garcia-Segura, Luis Miguel ; Nillni, Eduardo A. ; Mendez, Pablo ; Low, Malcolm J. ; Sótonyi, P. ; Friedman, Jeffrey M. ; Liu, Hongyan ; Pinto, Shirly ; Colmers, William F. ; Cone, Roger D. ; Horvath, Tamas L. / The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. In: Neuron. 2003 ; Vol. 37, No. 4. pp. 649-661.
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