Intracerebroventricular O-n-octanoylated ghrelin and its splice variant-induced feeding is blocked by insulin, independent of obestatin or CRF receptor, in satiated rats

Nutrition. 2012 Jul;28(7-8):812-20. doi: 10.1016/j.nut.2011.11.021. Epub 2012 Mar 30.

Abstract

Objective: The purpose of this study was to investigate the impact of intracerebroventricular (ICV) injection of the two endogenous forms of acyl ghrelin, O-n-octanoylated ghrelin and des-Gln¹⁴-ghrelin, on feeding behavior, as well as their interactions with insulin, obestatin, and corticotropin-releasing factor receptor (CRF-R) antagonist in the forebrain to influence food intake.

Methods: We examined the food intake in conscious, freely fed rats, which were chronically implanted with ICV catheters.

Results: O-n-octanoylated ghrelin and des-Gln¹⁴-ghrelin (0.1 nmol/rat) were equally potent in stimulating food intake in freely fed rats, up to 8 h after ICV injection (P < 0.05). In contrast, ICV administration of insulin (8 mU/rat), obestatin (2 nmol/rat), and astressin (2 nmol/rat), a specific CRF-R antagonist, did not modify feeding in freely fed rats. Furthermore, pretreatment with ICV insulin (P < 0.01), but not obestatin or astressin, at the abovementioned dose, blocked central acyl-ghrelin-induced hyperphagic effects.

Conclusion: ICV O-n-octanoylated ghrelin and its splice variant, des-Gln¹⁴-ghrelin, are equally potent to elicit food intake in freely fed rats, while these feeding-stimulating effects are opposed by insulin, but independent of obestatin and endogenous CRF-R in the forebrain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite Stimulants / administration & dosage
  • Appetite Stimulants / antagonists & inhibitors
  • Appetite Stimulants / metabolism
  • Behavior, Animal / drug effects
  • Catheters, Indwelling
  • Feeding Behavior / drug effects
  • Ghrelin / administration & dosage
  • Ghrelin / antagonists & inhibitors*
  • Ghrelin / metabolism
  • Hormone Antagonists / administration & dosage
  • Hormone Antagonists / pharmacology
  • Hyperphagia / metabolism*
  • Injections, Intraventricular
  • Insulin / administration & dosage
  • Insulin / metabolism*
  • Male
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Peptide Hormones / administration & dosage
  • Peptide Hormones / metabolism*
  • Prosencephalon / drug effects
  • Prosencephalon / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Time Factors

Substances

  • Appetite Stimulants
  • Ghrelin
  • Hormone Antagonists
  • Insulin
  • Nerve Tissue Proteins
  • Peptide Hormones
  • Receptors, Corticotropin-Releasing Hormone
  • ghrelin, des-Gln(14)-
  • obestatin, rat