Inhibition of Food Intake by Central Injection of Anti-Orexin Antibody in Fasted Rats

Biochem Biophys Res Commun. 2000 Jan 19;267(2):527-31. doi: 10.1006/bbrc.1999.1998.

Abstract

It has been shown that intracerebroventricular injection of synthetic orexins stimulated food intake in rats. This pharmacological evidence suggests that orexins may have a role for the central regulation of feeding. In the present study, we investigated the hypothesis of whether endogenous orexins indeed play a vital role in feeding behavior. An anti-orexin polyclonal antibody was used throughout the study. First, we examined the specificity of the antibody to orexin by Western blot analysis and immunohistochemistry. Next, the effects of central injection of the orexin antibody on food intake in 24-h-fasted rats were evaluated. Western blot analysis revealed that the orexin antibody detected synthetic orexin-A. Immunohistochemical study showed that orexin-positive neurons were identified only in the lateral hypothalamic area, in agreement with previous reports. Neither control antibody nor the orexin antibody preabsorbed with excess amount of orexin-A detected neurons, indicating that the orexin antibody is specific. Intracisternal but not intraperitoneal injection of the orexin antibody dose-dependently suppressed feeding. All these results suggest that immunoneutralization of endogenous orexins in the brain reduced food intake. In other words, we suggest that endogenous brain orexin may have a physiologically relevant action on feeding behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibody Specificity
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / immunology
  • Carrier Proteins / physiology*
  • Cisterna Magna
  • Eating / physiology*
  • Hypothalamic Area, Lateral / metabolism
  • Immunoglobulin G / administration & dosage
  • Immunohistochemistry
  • Injections, Intraventricular
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Neuropeptides / antagonists & inhibitors*
  • Neuropeptides / immunology
  • Neuropeptides / physiology*
  • Orexins
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antibodies
  • Carrier Proteins
  • Immunoglobulin G
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins