TY - JOUR
T1 - The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis
AU - Cowley, Michael A.
AU - Smith, Roy G.
AU - Diano, Sabrina
AU - Tschöp, Matthias
AU - Pronchuk, Nina
AU - Grove, Kevin L.
AU - Strasburger, Christian J.
AU - Bidlingmaier, Martin
AU - Esterman, Michael
AU - Heiman, Mark L.
AU - Garcia-Segura, Luis Miguel
AU - Nillni, Eduardo A.
AU - Mendez, Pablo
AU - Low, Malcolm J.
AU - Sotonyi, Peter
AU - Friedman, Jeffrey M.
AU - Liu, Hongyan
AU - Pinto, Shirly
AU - Colmers, William F.
AU - Cone, Roger D.
AU - Horvath, Tamas L.
N1 - Funding Information:
This work was supported by NIH grants DK-60711, RR-14451, MH-59847, DK-51730, DK-61619, DK-62202, MH-59847, and AG-018895, by the Canadian Institutes of Health Research grant MT 10520, and by Merck & Co. T.L.H. was an Albert Szent-Gyorgyi Fellow.
PY - 2003/2/20
Y1 - 2003/2/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037456519&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(03)00063-1
DO - 10.1016/S0896-6273(03)00063-1
M3 - Article
C2 - 12597862
AN - SCOPUS:0037456519
SN - 0896-6273
VL - 37
SP - 649
EP - 661
JO - Neuron
JF - Neuron
IS - 4
ER -