Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice

Diabetes. 2013 May;62(5):1500-4. doi: 10.2337/db12-0718. Epub 2012 Dec 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite Regulation* / drug effects
  • Behavior, Animal / drug effects
  • Feeding Behavior / drug effects
  • Ghrelin / antagonists & inhibitors
  • Ghrelin / metabolism
  • Hypothalamus / cytology
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism*
  • Injections, Intraventricular
  • Male
  • Melanocortins / agonists*
  • Melanocortins / antagonists & inhibitors
  • Melanocortins / metabolism
  • Melanocyte-Stimulating Hormones / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Natriuretic Peptide, C-Type / administration & dosage
  • Natriuretic Peptide, C-Type / antagonists & inhibitors
  • Natriuretic Peptide, C-Type / metabolism*
  • Nerve Tissue Proteins / administration & dosage
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptide Y / antagonists & inhibitors
  • Neuropeptide Y / metabolism
  • Protein Isoforms / agonists
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Protein Precursors / administration & dosage
  • Protein Precursors / antagonists & inhibitors
  • Protein Precursors / metabolism
  • Receptors, Melanocortin / agonists*
  • Receptors, Melanocortin / antagonists & inhibitors
  • Receptors, Melanocortin / metabolism
  • Signal Transduction* / drug effects
  • Up-Regulation / drug effects
  • alpha-MSH / metabolism

Substances

  • Ghrelin
  • Melanocortins
  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Protein Isoforms
  • Protein Precursors
  • Receptors, Melanocortin
  • natriuretic peptide precursor type C, mouse
  • Natriuretic Peptide, C-Type
  • SHU 9119
  • alpha-MSH
  • Melanocyte-Stimulating Hormones