Intracerebroventricular Administration of C-Type Natriuretic Peptide Suppresses Food Intake via Activation of the Melanocortin System in Mice
- Nobuko Yamada-Goto1⇑,
- Goro Katsuura1,
- Ken Ebihara1,
- Megumi Inuzuka1,
- Yukari Ochi1,
- Yui Yamashita1,
- Toru Kusakabe1,
- Akihiro Yasoda1,
- Noriko Satoh-Asahara2,
- Hiroyuki Ariyasu1,
- Kiminori Hosoda1 and
- Kazuwa Nakao1
- 1Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
- 2Clinical Research Institute, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
- Corresponding author: Nobuko Yamada-Goto,
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0718/-/DC1.
See accompanying commentary, p. 1379.
- Received May 31, 2012.
- Accepted November 7, 2012.
- © 2013 by the American Diabetes Association.
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