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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Neonatal ghrelin programs development of hypothalamic feeding circuits</title>
<author><name sortKey="Steculorum, Sophie M" sort="Steculorum, Sophie M" uniqKey="Steculorum S" first="Sophie M." last="Steculorum">Sophie M. Steculorum</name>
<affiliation><nlm:aff id="A1">The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Collden, Gustav" sort="Collden, Gustav" uniqKey="Collden G" first="Gustav" last="Collden">Gustav Collden</name>
<affiliation><nlm:aff id="A2">Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coupe, Berengere" sort="Coupe, Berengere" uniqKey="Coupe B" first="Berengere" last="Coupe">Berengere Coupe</name>
<affiliation><nlm:aff id="A1">The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Croizier, Sophie" sort="Croizier, Sophie" uniqKey="Croizier S" first="Sophie" last="Croizier">Sophie Croizier</name>
<affiliation><nlm:aff id="A1">The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lockie, Sarah" sort="Lockie, Sarah" uniqKey="Lockie S" first="Sarah" last="Lockie">Sarah Lockie</name>
<affiliation><nlm:aff id="A3">Department of Physiology, Monash University, Clayton, Victoria, Australia.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Andrews, Zane B" sort="Andrews, Zane B" uniqKey="Andrews Z" first="Zane B." last="Andrews">Zane B. Andrews</name>
<affiliation><nlm:aff id="A3">Department of Physiology, Monash University, Clayton, Victoria, Australia.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jarosch, Florian" sort="Jarosch, Florian" uniqKey="Jarosch F" first="Florian" last="Jarosch">Florian Jarosch</name>
<affiliation><nlm:aff id="A4">NOXXON Pharma AG, Berlin, Germany.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Klussmann, Sven" sort="Klussmann, Sven" uniqKey="Klussmann S" first="Sven" last="Klussmann">Sven Klussmann</name>
<affiliation><nlm:aff id="A4">NOXXON Pharma AG, Berlin, Germany.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bouret, Sebastien G" sort="Bouret, Sebastien G" uniqKey="Bouret S" first="Sebastien G." last="Bouret">Sebastien G. Bouret</name>
<affiliation><nlm:aff id="A1">The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25607843</idno>
<idno type="pmc">4319433</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319433</idno>
<idno type="RBID">PMC:4319433</idno>
<idno type="doi">10.1172/JCI73688</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">001928</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001928</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Neonatal ghrelin programs development of hypothalamic feeding circuits</title>
<author><name sortKey="Steculorum, Sophie M" sort="Steculorum, Sophie M" uniqKey="Steculorum S" first="Sophie M." last="Steculorum">Sophie M. Steculorum</name>
<affiliation><nlm:aff id="A1">The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Collden, Gustav" sort="Collden, Gustav" uniqKey="Collden G" first="Gustav" last="Collden">Gustav Collden</name>
<affiliation><nlm:aff id="A2">Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Coupe, Berengere" sort="Coupe, Berengere" uniqKey="Coupe B" first="Berengere" last="Coupe">Berengere Coupe</name>
<affiliation><nlm:aff id="A1">The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Croizier, Sophie" sort="Croizier, Sophie" uniqKey="Croizier S" first="Sophie" last="Croizier">Sophie Croizier</name>
<affiliation><nlm:aff id="A1">The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lockie, Sarah" sort="Lockie, Sarah" uniqKey="Lockie S" first="Sarah" last="Lockie">Sarah Lockie</name>
<affiliation><nlm:aff id="A3">Department of Physiology, Monash University, Clayton, Victoria, Australia.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Andrews, Zane B" sort="Andrews, Zane B" uniqKey="Andrews Z" first="Zane B." last="Andrews">Zane B. Andrews</name>
<affiliation><nlm:aff id="A3">Department of Physiology, Monash University, Clayton, Victoria, Australia.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jarosch, Florian" sort="Jarosch, Florian" uniqKey="Jarosch F" first="Florian" last="Jarosch">Florian Jarosch</name>
<affiliation><nlm:aff id="A4">NOXXON Pharma AG, Berlin, Germany.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Klussmann, Sven" sort="Klussmann, Sven" uniqKey="Klussmann S" first="Sven" last="Klussmann">Sven Klussmann</name>
<affiliation><nlm:aff id="A4">NOXXON Pharma AG, Berlin, Germany.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bouret, Sebastien G" sort="Bouret, Sebastien G" uniqKey="Bouret S" first="Sebastien G." last="Bouret">Sebastien G. Bouret</name>
<affiliation><nlm:aff id="A1">The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of Clinical Investigation</title>
<idno type="ISSN">0021-9738</idno>
<idno type="eISSN">1558-8238</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we evaluated the physiological and neurobiological contribution of ghrelin during development by specifically blocking ghrelin action during early postnatal development in mice. Ghrelin blockade in neonatal mice resulted in enhanced ARH neural projections and long-term metabolic effects, including increased body weight, visceral fat, and blood glucose levels and decreased leptin sensitivity. In addition, chronic administration of ghrelin during postnatal life impaired the normal development of ARH projections and caused metabolic dysfunction. Consistent with these observations, direct exposure of postnatal ARH neuronal explants to ghrelin blunted axonal growth and blocked the neurotrophic effect of the adipocyte-derived hormone leptin. Moreover, chronic ghrelin exposure in neonatal mice also attenuated leptin-induced STAT3 signaling in ARH neurons. Collectively, these data reveal that ghrelin plays an inhibitory role in the development of hypothalamic neural circuits and suggest that proper expression of ghrelin during neonatal life is pivotal for lifelong metabolic regulation.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Invest</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Clin. Invest</journal-id>
<journal-id journal-id-type="publisher-id">J CLIN INVEST</journal-id>
<journal-title-group><journal-title>The Journal of Clinical Investigation</journal-title>
</journal-title-group>
<issn pub-type="ppub">0021-9738</issn>
<issn pub-type="epub">1558-8238</issn>
<publisher><publisher-name>American Society for Clinical Investigation</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25607843</article-id>
<article-id pub-id-type="pmc">4319433</article-id>
<article-id pub-id-type="publisher-id">73688</article-id>
<article-id pub-id-type="doi">10.1172/JCI73688</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Neonatal ghrelin programs development of hypothalamic feeding circuits</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Steculorum</surname>
<given-names>Sophie M.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Collden</surname>
<given-names>Gustav</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Coupe</surname>
<given-names>Berengere</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Croizier</surname>
<given-names>Sophie</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lockie</surname>
<given-names>Sarah</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Andrews</surname>
<given-names>Zane B.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jarosch</surname>
<given-names>Florian</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Klussmann</surname>
<given-names>Sven</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bouret</surname>
<given-names>Sebastien G.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.</aff>
<aff id="A2"><label>2</label>
Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, France.</aff>
<aff id="A3"><label>3</label>
Department of Physiology, Monash University, Clayton, Victoria, Australia.</aff>
<aff id="A4"><label>4</label>
NOXXON Pharma AG, Berlin, Germany.</aff>
<author-notes><corresp>Address correspondence to: Sebastien G. Bouret, The Saban Research Institute, Developmental Neuroscience Program, Children’s Hospital Los Angeles, University of Southern California, 4650 Sunset Boulevard, MS#135, Los Angeles, California 90027, USA. Phone: 323.361.8743; E-mail: <email>sbouret@chla.usc.edu</email>
.</corresp>
<fn><p><bold>Authorship note:</bold>
Gustav Collden, Berengere Coupe, and Sophie Croizier contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>20</day>
<month>1</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="ppub"><day>2</day>
<month>2</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>2</day>
<month>5</month>
<year>2015</year>
</pub-date>
<pmc-comment> PMC Release delay is 3 months and 0 days and was based on the . </pmc-comment>
<volume>125</volume>
<issue>2</issue>
<fpage>846</fpage>
<lpage>858</lpage>
<history><date date-type="received"><day>10</day>
<month>10</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>6</day>
<month>11</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2015, American Society for Clinical Investigation</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>American Society for Clinical Investigation</copyright-holder>
</permissions>
<abstract><p>A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we evaluated the physiological and neurobiological contribution of ghrelin during development by specifically blocking ghrelin action during early postnatal development in mice. Ghrelin blockade in neonatal mice resulted in enhanced ARH neural projections and long-term metabolic effects, including increased body weight, visceral fat, and blood glucose levels and decreased leptin sensitivity. In addition, chronic administration of ghrelin during postnatal life impaired the normal development of ARH projections and caused metabolic dysfunction. Consistent with these observations, direct exposure of postnatal ARH neuronal explants to ghrelin blunted axonal growth and blocked the neurotrophic effect of the adipocyte-derived hormone leptin. Moreover, chronic ghrelin exposure in neonatal mice also attenuated leptin-induced STAT3 signaling in ARH neurons. Collectively, these data reveal that ghrelin plays an inhibitory role in the development of hypothalamic neural circuits and suggest that proper expression of ghrelin during neonatal life is pivotal for lifelong metabolic regulation.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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