Nesfatin-1-Regulated Oxytocinergic Signaling in the Paraventricular Nucleus Causes Anorexia through a Leptin-Independent Melanocortin Pathway

被引：312

作者：

Maejima, Yuko ^{[1
]}

Sedbazar, Udval ^{[1
]}

Suyama, Shigetomo ^{[1
]}

Kohno, Daisuke ^{[1
]}

Onaka, Tatsushi ^{[2
]}

Takano, Eisuke ^{[1
]}

Yoshida, Natsu ^{[1
]}

Koike, Masato ^{[3
]}

Uchiyama, Yasuo ^{[3
]}

Fujiwara, Ken ^{[4
]}

Yashiro, Takashi ^{[4
]}

Horvath, Tamas L. ^{[5
]}

Dietrich, Marcelo O. ^{[5
,6
]}

Tanaka, Shigeyasu ^{[7
]}

Dezaki, Katsuya ^{[1
]}

Oh-I, Shinsuke ^{[8
]}

Hashimoto, Koushi ^{[8
]}

Shimizu, Hiroyuki ^{[8
]}

Nakata, Masanori ^{[1
]}

Mori, Masatomo ^{[8
]}

Yada, Toshihiko ^{[1
]}

机构：

[1] Jichi Med Univ, Sch Med, Dept Physiol, Div Integrat Physiol, Shimotsuke, Tochigi 3290498, Japan

[2] Jichi Med Univ, Sch Med, Dept Physiol, Div Brain & Neurophysiol, Shimotsuke, Tochigi 3290498, Japan

[3] Juntendo Univ, Grad Sch Med, Dept Cell Biol & Neurosci, Bunkyo Ku, Tokyo 1138421, Japan

[4] Jichi Med Univ, Sch Med, Dept Anat, Div Histol, Shimotsuke, Tochigi 3290498, Japan

[5] Yale Univ, Sch Med, Comparat Med Sect, Program Cell & Neurobiol Energy Metab, New Haven, CT 06520 USA

[6] Univ Fed Rio Grande do Sul, Dept Biochem, Programa Posgrad Bioquim, BR-90035 Porto Alegre, RS, Brazil

[7] Shizuoka Univ, Fac Sci, Dept Biol, Shizuoka 4228529, Japan

[8] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Gunma 3718511, Japan

来源：

CELL METABOLISM | 2009年 / 10卷 / 05期

基金：

日本学术振兴会; 美国国家卫生研究院;

关键词：

NERVOUS-SYSTEM CONTROL; ARCUATE NUCLEUS; SOLITARY TRACT; FOOD-INTAKE; PROOPIOMELANOCORTIN NEURONS; BRAIN OXYTOCIN; NEUROPEPTIDE-Y; RECEPTOR; PITUITARY; RELEASE;

D O I：

10.1016/j.cmet.2009.09.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：355 / 365

页数：11

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