title: Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice.
abstract: C-type natriuretic peptide (CNP) and its receptor are abundantly distributed in the brain, especially in the arcuate nucleus (ARC) of the hypothalamus associated with regulating energy homeostasis. To elucidate the possible involvement of CNP in energy regulation, we examined the effects of intracerebroventricular administration of CNP on food intake in mice. The intracerebroventricular administration of CNP-22 and CNP-53 significantly suppressed food intake on 4-h refeeding after 48-h fasting. Next, intracerebroventricular administration of CNP-22 and CNP-53 significantly decreased nocturnal food intake. The increment of food intake induced by neuropeptide Y and ghrelin was markedly suppressed by intracerebroventricular administration of CNP-22 and CNP-53. When SHU9119, an antagonist for melanocortin-3 and melanocortin-4 receptors, was coadministered with CNP-53, the suppressive effect of CNP-53 on refeeding after 48-h fasting was significantly attenuated by SHU9119. Immunohistochemical analysis revealed that intracerebroventricular administration of CNP-53 markedly increased the number of c-Fos-positive cells in the ARC, paraventricular nucleus, dorsomedial hypothalamus, ventromedial hypothalamic nucleus, and lateral hypothalamus. In particular, c-Fos-positive cells in the ARC after intracerebroventricular administration of CNP-53 were coexpressed with α-melanocyte-stimulating hormone immunoreactivity. These results indicated that intracerebroventricular administration of CNP induces an anorexigenic action, in part, via activation of the melanocortin system.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan. nobukito@kuhp.kyoto-u.ac.jp
authors.forename: Nobuko
authors.initials: N
authors.lastname: Yamada-Goto
authors.forename: Goro
authors.initials: G
authors.lastname: Katsuura
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Megumi
authors.initials: M
authors.lastname: Inuzuka
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ochi
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yasoda
authors.forename: Noriko
authors.initials: N
authors.lastname: Satoh-Asahara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ariyasu
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D053486:Melanocortins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism; D020033:Protein Isoforms / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D011498:Protein Precursors / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D054439:Ghrelin; D053486:Melanocortins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D020033:Protein Isoforms; D011498:Protein Precursors; D044101:Receptors, Melanocortin; C553310:natriuretic peptide precursor type C, mouse; D020098:Natriuretic Peptide, C-Type; C103272:SHU 9119; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones