A Natural Variant of Obestatin, Q90L, Inhibits Ghrelin's Action on Food Intake and GH Secretion and Targets NPY and GHRH Neurons in Mice

Hassouna, Rim, Zizzari, Philippe, Viltart, Odile, Yang, Seung-Kwon, Gardette, Robert, Videau, Catherine, Badoer, Emilio, Epelbaum, Jacques and Tolle, Virginie (2012) A Natural Variant of Obestatin, Q90L, Inhibits Ghrelin's Action on Food Intake and GH Secretion and Targets NPY and GHRH Neurons in Mice. Plos One, 7 12: e51135-1-e51135-9. doi:10.1371/journal.pone.0051135

Author Hassouna, Rim
Zizzari, Philippe
Viltart, Odile
Yang, Seung-Kwon
Gardette, Robert
Videau, Catherine
Badoer, Emilio
Epelbaum, Jacques
Tolle, Virginie
Title A Natural Variant of Obestatin, Q90L, Inhibits Ghrelin's Action on Food Intake and GH Secretion and Targets NPY and GHRH Neurons in Mice
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-12
Sub-type Article (original research)
DOI 10.1371/journal.pone.0051135
Open Access Status DOI
Volume 7
Issue 12
Start page e51135-1
End page e51135-9
Total pages 9
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2013
Language eng
Formatted abstract
Background: Ghrelin and obestatin are two gut-derived peptides originating from the same ghrelin/obestatin prepropeptide gene (GHRL). While ghrelin stimulates growth hormone (GH) secretion and food intake and inhibits caminobutyric-acid synaptic transmission onto GHRH (Growth Hormone Releasing Hormone) neurons, obestatin blocks these effects. In Humans, GHRL gene polymorphisms have been associated with pathologies linked to an unbalanced energy homeostasis. We hypothesized that one polymorphism located in the obestatin sequence (Q to L substitution in position 90 of the ghrelin/obestatin prepropeptide, rs4684677) may impact on the function of obestatin. In the present study, we tested the activity of native and Q90L obestatin to modulate ghrelin-induced food intake, GH secretion, cFos activity in GHRH and
Neuropeptide Y (NPY) neurons and c-aminobutyric-acid activity onto GHRH neurons.
Methodology/Principal findings: Food intake, GH secretion and electrophysiological recordings were assessed in C57BL/6 mice. cFos activity was measured in NPY-Renilla-GFP and GHRH-eGFP mice. Mice received saline, ghrelin or ghrelin
combined to native or Q90L obestatin (30 nmol each) in the early light phase. Ghrelin stimulation of food intake and GH secretion varied considerably among individual mice with 59–77% eliciting a robust response. In these high-responders,
ghrelin-induced food intake and GH secretion were reduced equally by native and Q90L obestatin. In contrast to in vivo observations, Q90L was slightly more efficient than native obestatin in inhibiting ghrelin-induced cFos activation within the
hypothalamic arcuate nucleus and the nucleus tractus solitarius of the brainstem. After ghrelin injection, 26% of NPY neurons in the arcuate nucleus expressed cFos protein and this number was significantly reduced by co-administration of
Q90L obestatin. Q90L was also more potent that native obestatin in reducing ghrelin-induced inhibition of c-aminobutyricacid synaptic transmission onto GHRH neurons.
Conclusions/Significance: These data support the hypothesis that Q90L obestatin partially blocks ghrelin-induced food intake and GH secretion by acting through NPY and GHRH neurons.
Keyword Growth hormone secretagogue receptor
Hypothalamic Arcuate Nucleus
Green Fluorescent Protein
Neuropeptide-Y Neurons
Family Trios Analysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 14 times in Scopus Article | Citations
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