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, Peter Sotonyi, Jeffrey M. Friedman, Hongyan Liu, Shirly Pinto, William F. Colmers, Roger D. ConeTamas L. Horvath

    Research output: Contribution to journalArticlepeer-review

    1266 Scopus citations

    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 (US)
    Pages (from-to)649-661
    Number of pages13
    JournalNeuron
    Volume37
    Issue number4
    DOIs
    StatePublished - Feb 20 2003

    ASJC Scopus subject areas

    • Neuroscience(all)

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