A Natural Variant of Obestatin, Q90L, Inhibits Ghrelin's Action on Food Intake and GH Secretion and Targets NPY and GHRH Neurons in Mice
Identifieur interne : 005499 ( Main/Exploration ); précédent : 005498; suivant : 005500A Natural Variant of Obestatin, Q90L, Inhibits Ghrelin's Action on Food Intake and GH Secretion and Targets NPY and GHRH Neurons in Mice
Auteurs : Rim Hassouna [France] ; Philippe Zizzari [France] ; Odile Viltart [France] ; Seung-Kwon Yang [Australie] ; Robert Gardette [France] ; Catherine Videau [France] ; Emilio Badoer [Australie] ; Jacques Epelbaum [France] ; Virginie Tolle [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Ghrelin and obestatin are two gut-derived peptides originating from the same ghrelin/obestatin prepropeptide gene (
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
These data support the hypothesis that Q90L obestatin partially blocks ghrelin-induced food intake and GH secretion by acting through NPY and GHRH neurons.
Url:
DOI: 10.1371/journal.pone.0051135
PubMed: 23251435
PubMed Central: 3519497
Affiliations:
- Australie, France
- Hauts-de-France, Nord-Pas-de-Calais, Île-de-France
- Lille, Paris
- Université Paris-Descartes
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Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Zizzari, Philippe" sort="Zizzari, Philippe" uniqKey="Zizzari P" first="Philippe" last="Zizzari">Philippe Zizzari</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Viltart, Odile" sort="Viltart, Odile" uniqKey="Viltart O" first="Odile" last="Viltart">Odile Viltart</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>UMR 837 INSERM, Laboratoire “Développement et Plasticité du Cerveau Postnatal”, Centre de Recherches JPARC, Lille and Université Lille Nord de France (USTL- Lille 1), Lille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>UMR 837 INSERM, Laboratoire “Développement et Plasticité du Cerveau Postnatal”, Centre de Recherches JPARC, Lille and Université Lille Nord de France (USTL- Lille 1), Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Yang, Seung Kwon" sort="Yang, Seung Kwon" uniqKey="Yang S" first="Seung-Kwon" last="Yang">Seung-Kwon Yang</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>School of Biomedical Sciences, The University of Queensland, Skerman Building (65), St Lucia, Queensland, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biomedical Sciences, The University of Queensland, Skerman Building (65), St Lucia, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Gardette, Robert" sort="Gardette, Robert" uniqKey="Gardette R" first="Robert" last="Gardette">Robert Gardette</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Videau, Catherine" sort="Videau, Catherine" uniqKey="Videau C" first="Catherine" last="Videau">Catherine Videau</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Badoer, Emilio" sort="Badoer, Emilio" uniqKey="Badoer E" first="Emilio" last="Badoer">Emilio Badoer</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>School of Medical Sciences and Health Innovations Research Institute, RMIT University, Bundoora, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medical Sciences and Health Innovations Research Institute, RMIT University, Bundoora, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Epelbaum, Jacques" sort="Epelbaum, Jacques" uniqKey="Epelbaum J" first="Jacques" last="Epelbaum">Jacques Epelbaum</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Tolle, Virginie" sort="Tolle, Virginie" uniqKey="Tolle V" first="Virginie" last="Tolle">Virginie Tolle</name><affiliation wicri:level="4"><nlm:aff id="aff1"><addr-line>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Ghrelin and obestatin are two gut-derived peptides originating from the same ghrelin/obestatin prepropeptide gene (<italic>GHRL</italic>). While ghrelin stimulates growth hormone (GH) secretion and food intake and inhibits γ-aminobutyric-acid synaptic transmission onto GHRH (Growth Hormone Releasing Hormone) neurons, obestatin blocks these effects. In Humans, <italic>GHRL</italic> 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 γ-aminobutyric-acid activity onto GHRH neurons.</p></sec><sec><title>Methodology/Principal findings</title><p>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 <italic>in vivo</italic> 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 γ-aminobutyric-acid synaptic transmission onto GHRH neurons.</p></sec><sec><title>Conclusions/Significance</title><p>These data support the hypothesis that Q90L obestatin partially blocks ghrelin-induced food intake and GH secretion by acting through NPY and GHRH neurons.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kojima, M" uniqKey="Kojima M">M Kojima</name></author><author><name sortKey="Hosoda, H" uniqKey="Hosoda H">H Hosoda</name></author><author><name sortKey="Date, Y" uniqKey="Date Y">Y Date</name></author><author><name sortKey="Nakazato, M" uniqKey="Nakazato M">M Nakazato</name></author><author><name sortKey="Matsuo, H" uniqKey="Matsuo H">H Matsuo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tomasetto, C" uniqKey="Tomasetto C">C Tomasetto</name></author><author><name sortKey="Karam, Sm" 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Kobelt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Stengel, A" uniqKey="Stengel A">A Stengel</name></author><author><name sortKey="Goebel, M" uniqKey="Goebel M">M Goebel</name></author><author><name sortKey="Martinez, V" uniqKey="Martinez V">V Martinez</name></author><author><name sortKey="Gourcerol, G" uniqKey="Gourcerol G">G Gourcerol</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, Y" uniqKey="Yu Y">Y Yu</name></author><author><name sortKey="South, T" uniqKey="South T">T South</name></author><author><name sortKey="Huang, Xf" uniqKey="Huang X">XF Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steyn, Fj" uniqKey="Steyn F">FJ Steyn</name></author><author><name sortKey="Huang, L" uniqKey="Huang L">L Huang</name></author><author><name sortKey="Ngo, St" uniqKey="Ngo S">ST Ngo</name></author><author><name sortKey="Leong, Jw" uniqKey="Leong J">JW Leong</name></author><author><name sortKey="Tan, Hy" uniqKey="Tan H">HY Tan</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Hauts-de-France</li><li>Nord-Pas-de-Calais</li><li>Île-de-France</li></region><settlement><li>Lille</li><li>Paris</li></settlement><orgName><li>Université Paris-Descartes</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Hassouna, Rim" sort="Hassouna, Rim" uniqKey="Hassouna R" first="Rim" last="Hassouna">Rim Hassouna</name></region><name sortKey="Epelbaum, Jacques" sort="Epelbaum, Jacques" uniqKey="Epelbaum J" first="Jacques" last="Epelbaum">Jacques Epelbaum</name><name sortKey="Gardette, Robert" sort="Gardette, Robert" uniqKey="Gardette R" first="Robert" last="Gardette">Robert Gardette</name><name sortKey="Tolle, Virginie" sort="Tolle, Virginie" uniqKey="Tolle V" first="Virginie" last="Tolle">Virginie Tolle</name><name sortKey="Videau, Catherine" sort="Videau, Catherine" uniqKey="Videau C" first="Catherine" last="Videau">Catherine Videau</name><name sortKey="Viltart, Odile" sort="Viltart, Odile" uniqKey="Viltart O" first="Odile" last="Viltart">Odile Viltart</name><name sortKey="Zizzari, Philippe" sort="Zizzari, Philippe" uniqKey="Zizzari P" first="Philippe" last="Zizzari">Philippe Zizzari</name></country><country name="Australie"><noRegion><name sortKey="Yang, Seung Kwon" sort="Yang, Seung Kwon" uniqKey="Yang S" first="Seung-Kwon" last="Yang">Seung-Kwon Yang</name></noRegion><name sortKey="Badoer, Emilio" sort="Badoer, Emilio" uniqKey="Badoer E" first="Emilio" last="Badoer">Emilio Badoer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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