title: The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.
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.
authors.affiliation: The Vollum Institute, Oregon Health & Science University, Portland, OR 97201, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cowley
authors.forename: Roy G
authors.initials: RG
authors.lastname: Smith
authors.forename: Sabrina
authors.initials: S
authors.lastname: Diano
authors.forename: Matthias
authors.initials: M
authors.lastname: Tschöp
authors.forename: Nina
authors.initials: N
authors.lastname: Pronchuk
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Strasburger
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: Michael
authors.initials: M
authors.lastname: Esterman
authors.forename: Mark L
authors.initials: ML
authors.lastname: Heiman
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Nillni
authors.forename: Pablo
authors.initials: P
authors.lastname: Mendez
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Low
authors.forename: Peter
authors.initials: P
authors.lastname: Sotonyi
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Friedman
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.forename: Shirly
authors.initials: S
authors.lastname: Pinto
authors.forename: William F
authors.initials: WF
authors.lastname: Colmers
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cone
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
mesh_terms: 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
chemical_list: 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