title: Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway.
abstract: The hypothalamic paraventricular nucleus (PVN) functions as a center to integrate various neuronal activities for regulating feeding behavior. Nesfatin-1, a recently discovered anorectic molecule, is localized in the PVN. However, the anorectic neural pathway of nesfatin-1 remains unknown. Here we show that central injection of nesfatin-1 activates the PVN and brain stem nucleus tractus solitarius (NTS). In the PVN, nesfatin-1 targets both magnocellular and parvocellular oxytocin neurons and nesfatin-1 neurons themselves and stimulates oxytocin release. Immunoelectron micrographs reveal nesfatin-1 specifically in the secretory vesicles of PVN neurons, and immunoneutralization against endogenous nesfatin-1 suppresses oxytocin release in the PVN, suggesting paracrine/autocrine actions of nesfatin-1. Nesfatin-1-induced anorexia is abolished by an oxytocin receptor antagonist. Moreover, oxytocin terminals are closely associated with and oxytocin activates pro-opiomelanocortin neurons in the NTS. Oxytocin induces melanocortin-dependent anorexia in leptin-resistant Zucker-fatty rats. The present results reveal the nesfatin-1-operative oxytocinergic signaling in the PVN that triggers leptin-independent melanocortin-mediated anorexia.
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Maejima
authors.forename: Udval
authors.initials: U
authors.lastname: Sedbazar
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Suyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohno
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Onaka
authors.forename: Eisuke
authors.initials: E
authors.lastname: Takano
authors.forename: Natsu
authors.initials: N
authors.lastname: Yoshida
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Ken
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Takashi
authors.initials: T
authors.lastname: Yashiro
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
authors.forename: Marcelo O
authors.initials: MO
authors.lastname: Dietrich
authors.forename: Shigeyasu
authors.initials: S
authors.lastname: Tanaka
authors.forename: Katsuya
authors.initials: K
authors.lastname: Dezaki
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Oh-I
authors.forename: Koushi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakata
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D000818:Animals; D000855:Anorexia / Q000378:metabolism; D019898:Autocrine Communication; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D020738:Leptin / Q000378:metabolism; D053486:Melanocortins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055099:Neuroendocrine Cells / Q000378:metabolism; D000080866:Nucleobindins; D010121:Oxytocin / Q000378:metabolism*; D019899:Paracrine Communication; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction / Q000502:physiology*; D017552:Solitary Nucleus / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D053486:Melanocortins; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D010121:Oxytocin; D011333:Pro-Opiomelanocortin