Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar increases in food intake and patterns of hypothalamic gene expression.
The gut peptide ghrelin has been shown to stimulate food intake after both peripheral and central administration, and the hypothalamic arcuate nucleus has been proposed to be the major site for mediating this feeding stimulatory action. Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin administration has been shown to potently stimulate feeding, suggesting that there may be other sites for ghrelin action. In the present study, we have further assessed potential sites for ghrelin action by comparing the ability of lateral and fourth ventricular ghrelin administration to stimulate food intake and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2 nmol) in the lateral or fourth ventricle significantly increased food intake in the first 4 h after injection, with no ventricle-dependent differences in degree or time course of hyperphagia. One nanomole of ghrelin into either the lateral or fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y mRNA expression. Expression levels of agouti-related peptide or proopiomelanocortin mRNA were not affected by ghrelin administration. These data demonstrate that ghrelin can affect food intake and hypothalamic gene expression through interactions at multiple brain sites.
Kinzig
Kimberly P
KP
Johns Hopkins School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, USA. kkinzig@psych.purdue.edu
Scott
Karen A
KA
Hyun
Jayson
J
Bi
Sheng
S
Moran
Timothy H
TH
D054369:Agouti-Related Protein; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D020546:Fourth Ventricle / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D054439:Ghrelin; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D020547:Lateral Ventricles / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics; D036361:Peptide Hormones / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D054369:Agouti-Related Protein; D054439:Ghrelin; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D036361:Peptide Hormones; D011333:Pro-Opiomelanocortin