Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice
Identifieur interne : 003007 ( Pmc/Corpus ); précédent : 003006; suivant : 003008Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice
Auteurs : Noelia Escobedo ; Steven T. Proulx ; Sinem Karaman ; Miriam E. Dillard ; Nicole Johnson ; Michael Detmar ; Guillermo OliverSource :
- JCI Insight [ 2379-3708 ] ; ????.
Abstract
Url:
DOI: 10.1172/jci.insight.85096
PubMed: 26973883
PubMed Central: 4786184
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PMC:4786184Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice</title><author><name sortKey="Escobedo, Noelia" sort="Escobedo, Noelia" uniqKey="Escobedo N" first="Noelia" last="Escobedo">Noelia Escobedo</name><affiliation><nlm:aff id="A1">Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Proulx, Steven T" sort="Proulx, Steven T" uniqKey="Proulx S" first="Steven T." last="Proulx">Steven T. Proulx</name><affiliation><nlm:aff id="A2">Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Karaman, Sinem" sort="Karaman, Sinem" uniqKey="Karaman S" first="Sinem" last="Karaman">Sinem Karaman</name><affiliation><nlm:aff id="A2">Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Dillard, Miriam E" sort="Dillard, Miriam E" uniqKey="Dillard M" first="Miriam E." last="Dillard">Miriam E. Dillard</name><affiliation><nlm:aff id="A1">Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Johnson, Nicole" sort="Johnson, Nicole" uniqKey="Johnson N" first="Nicole" last="Johnson">Nicole Johnson</name><affiliation><nlm:aff id="A1">Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><affiliation><nlm:aff id="A2">Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Oliver, Guillermo" sort="Oliver, Guillermo" uniqKey="Oliver G" first="Guillermo" last="Oliver">Guillermo Oliver</name><affiliation><nlm:aff id="A1">Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26973883</idno><idno type="pmc">4786184</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786184</idno><idno type="RBID">PMC:4786184</idno><idno type="doi">10.1172/jci.insight.85096</idno><date when="????">????</date><idno type="wicri:Area/Pmc/Corpus">003007</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003007</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice</title><author><name sortKey="Escobedo, Noelia" sort="Escobedo, Noelia" uniqKey="Escobedo N" first="Noelia" last="Escobedo">Noelia Escobedo</name><affiliation><nlm:aff id="A1">Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Proulx, Steven T" sort="Proulx, Steven T" uniqKey="Proulx S" first="Steven T." last="Proulx">Steven T. Proulx</name><affiliation><nlm:aff id="A2">Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Karaman, Sinem" sort="Karaman, Sinem" uniqKey="Karaman S" first="Sinem" last="Karaman">Sinem Karaman</name><affiliation><nlm:aff id="A2">Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Dillard, Miriam E" sort="Dillard, Miriam E" uniqKey="Dillard M" first="Miriam E." last="Dillard">Miriam E. Dillard</name><affiliation><nlm:aff id="A1">Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Johnson, Nicole" sort="Johnson, Nicole" uniqKey="Johnson N" first="Nicole" last="Johnson">Nicole Johnson</name><affiliation><nlm:aff id="A1">Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</nlm:aff></affiliation></author><author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><affiliation><nlm:aff id="A2">Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Oliver, Guillermo" sort="Oliver, Guillermo" uniqKey="Oliver G" first="Guillermo" last="Oliver">Guillermo Oliver</name><affiliation><nlm:aff id="A1">Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</nlm:aff></affiliation></author></analytic><series><title level="j">JCI Insight</title><idno type="eISSN">2379-3708</idno><imprint><date when="????">????</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><italic>Prox1</italic> heterozygous mice have a defective lymphatic vasculature and develop late-onset obesity. Chyle abnormally leaks from those vessels, accumulates in the surrounding tissues, and causes an increase in adipose tissue. We characterized the lymphatics of <italic>Prox1</italic><sup>+/–</sup> mice to determine whether the extent of obesity correlated with the severity of lymphatic defects. The lymphatic vasculature in <italic>Prox1</italic><sup>+/–</sup> mice exhibited reduced tracer clearance from the ear skin, dysfunctional perfusion of the lower legs, and reduced tracer uptake into the deep lymphatic collectors during mechanostimulation prior to the onset of obesity. Ear lymphatic vessels and leg collectors in <italic>Prox1<sup>+/–</sup></italic> mice were disorganized and irregular, further confirming that defective lymphatic vessels are associated with obesity in <italic>Prox1<sup>+/–</sup></italic> mice. We now provide conclusive in vivo evidence that demonstrates that leaky lymphatics mediate obesity in <italic>Prox1<sup>+/–</sup></italic> mice, as restoration of lymphatic vasculature function was sufficient to rescue the obesity features in <italic>Prox1</italic><sup>+/–</sup> mice. Finally, depth-lipomic profiling of lymph contents showed that free fatty acids induce adipogenesis in vitro.</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">JCI Insight</journal-id><journal-id journal-id-type="iso-abbrev">JCI Insight</journal-id><journal-id journal-id-type="publisher-id">JCI Insight</journal-id><journal-title-group><journal-title>JCI Insight</journal-title></journal-title-group><issn pub-type="epub">2379-3708</issn><publisher><publisher-name>American Society for Clinical Investigation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26973883</article-id><article-id pub-id-type="pmc">4786184</article-id><article-id pub-id-type="publisher-id">85096</article-id><article-id pub-id-type="doi">10.1172/jci.insight.85096</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-0743-2258</contrib-id><name><surname>Escobedo</surname><given-names>Noelia</given-names></name><email>noelia.escobedo@stjude.org</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Proulx</surname><given-names>Steven T.</given-names></name><email>steven.proulx@pharma.ethz.ch</email><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-0719-1773</contrib-id><name><surname>Karaman</surname><given-names>Sinem</given-names></name><email>sinem.karaman@pharma.ethz.ch</email><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dillard</surname><given-names>Miriam E.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Johnson</surname><given-names>Nicole</given-names></name><email>ackernic@berkeleyprep.org</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Detmar</surname><given-names>Michael</given-names></name><email>michael.detmar@pharma.ethz.ch</email><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Oliver</surname><given-names>Guillermo</given-names></name><email>guillermo.oliver@northwestern.edu</email><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.</aff><aff id="A2"><label>2</label>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.</aff><author-notes><corresp>Address correspondence to: Guillermo Oliver, Northwestern University Feinberg School of Medicine, 303 East Superior Street, 10-107, Chicago, Illinois 60611, USA. Phone: 312.503.1651; E-mail: <email>guillermo.oliver@northwestern.edu</email>.</corresp><fn><p><bold>Authorship note:</bold> N. Escobedo, S.T. Proulx, and S. Karaman contributed equally to this work.</p></fn></author-notes><pub-date date-type="pub" publication-format="electronic" iso-8601-date="2016-02-25"><day>25</day><month>2</month><year>2016</year></pub-date><pub-date date-type="collection" publication-format="electronic" iso-8601-date="2016-02-25"><day>25</day><month>2</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>25</day><month>2</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and
0 days and was based on the
<volume>1</volume><issue>2</issue><elocation-id>e85096</elocation-id><history><date date-type="received"><day>12</day><month>10</month><year>2015</year></date><date date-type="accepted"><day>22</day><month>1</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016, American Society for Clinical Investigation</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>American Society for Clinical Investigation</copyright-holder></permissions><self-uri xlink:href="https://insight.jci.org/articles/view/85096">This article is available online at https://insight.jci.org/articles/view/85096</self-uri><abstract><p><italic>Prox1</italic> heterozygous mice have a defective lymphatic vasculature and develop late-onset obesity. Chyle abnormally leaks from those vessels, accumulates in the surrounding tissues, and causes an increase in adipose tissue. We characterized the lymphatics of <italic>Prox1</italic><sup>+/–</sup> mice to determine whether the extent of obesity correlated with the severity of lymphatic defects. The lymphatic vasculature in <italic>Prox1</italic><sup>+/–</sup> mice exhibited reduced tracer clearance from the ear skin, dysfunctional perfusion of the lower legs, and reduced tracer uptake into the deep lymphatic collectors during mechanostimulation prior to the onset of obesity. Ear lymphatic vessels and leg collectors in <italic>Prox1<sup>+/–</sup></italic> mice were disorganized and irregular, further confirming that defective lymphatic vessels are associated with obesity in <italic>Prox1<sup>+/–</sup></italic> mice. We now provide conclusive in vivo evidence that demonstrates that leaky lymphatics mediate obesity in <italic>Prox1<sup>+/–</sup></italic> mice, as restoration of lymphatic vasculature function was sufficient to rescue the obesity features in <italic>Prox1</italic><sup>+/–</sup> mice. Finally, depth-lipomic profiling of lymph contents showed that free fatty acids induce adipogenesis in vitro.</p></abstract><abstract abstract-type="toc"><p>Lymphatic vasculature defects in mice heterozygous for <italic>Prox1</italic> lead to late onset obesity, which may be triggered by adipogenic factors in leaking chyle.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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