The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.
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.
Cowley
Michael A
MA
The Vollum Institute, Oregon Health & Science University, Portland, OR 97201, USA.
Smith
Roy G
RG
Diano
Sabrina
S
Tschöp
Matthias
M
Pronchuk
Nina
N
Grove
Kevin L
KL
Strasburger
Christian J
CJ
Bidlingmaier
Martin
M
Esterman
Michael
M
Heiman
Mark L
ML
Garcia-Segura
Luis Miguel
LM
Nillni
Eduardo A
EA
Mendez
Pablo
P
Low
Malcolm J
MJ
Sotonyi
Peter
P
Friedman
Jeffrey M
JM
Liu
Hongyan
H
Pinto
Shirly
S
Colmers
William F
WF
Cone
Roger D
RD
Horvath
Tamas L
TL
D054369:Agouti-Related Protein; D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D054439:Ghrelin; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009415:Nerve Net / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009478:Neuropeptide Y / Q000096:biosynthesis; D009928:Organ Specificity; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D036361:Peptide Hormones / Q000378:metabolism* / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D011485:Protein Binding / Q000502:physiology; D014176:Protein Biosynthesis; D011506:Proteins; D051381:Rats
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D054439:Ghrelin; D036341:Intercellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009478:Neuropeptide Y; D036361:Peptide Hormones; D011506:Proteins; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone