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

1290 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
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis'. Together they form a unique fingerprint.

Cite this