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1000 Titel
  • New Function for an Old Enzyme: NEP Deficient Mice Develop Late-Onset Obesity
1000 Autor/in
  1. Becker, Matthias |
  2. Siems, Wolf-Eberhard |
  3. Kluge, Reinhart |
  4. Gembardt, Florian |
  5. Schultheiss, Heinz-Peter |
  6. Schirner, Michael |
  7. Walther, Thomas |
1000 Erscheinungsjahr 2010
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2010-09-16
1000 Erschienen in
1000 Quellenangabe
  • 5(9): e12793
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2010
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1371/journal.pone.0012793 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940827/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND: According to the World Health Organization (WHO) there is a pandemic of obesity with approximately 300 million people being obese. Typically, human obesity has a polygenetic causation. Neutral endopeptidase (NEP), also known as neprilysin, is considered to be one of the key enzymes in the metabolism of many active peptide hormones. METHODOLOGY/PRINCIPAL FINDINGS: An incidental observation in NEP-deficient mice was a late-onset excessive gain in body weight exclusively from a ubiquitous accumulation of fat tissue. In accord with polygenetic human obesity, mice were characterized by deregulation of lipid metabolism, higher blood glucose levels, with impaired glucose tolerance. The key role of NEP in determining body mass was confirmed by the use of the NEP inhibitor candoxatril in wild-type mice that increased body weight due to increased food intake. This is a peripheral and not a central NEP action on the switch for appetite control, since candoxatril cannot cross the blood-brain barrier. Furthermore, we demonstrated that inhibition of NEP in mice with cachexia delayed rapid body weight loss. Thus, lack in NEP activity, genetically or pharmacologically, leads to a gain in body fat. CONCLUSIONS/SIGNIFICANCE: In the present study, we have identified NEP to be a crucial player in the development of obesity. NEP-deficient mice start to become obese under a normocaloric diet in an age of 6–7 months and thus are an ideal model for the typical human late-onset obesity. Therefore, the described obesity model is an ideal tool for research on development, molecular mechanisms, diagnosis, and therapy of the pandemic obesity.
1000 Sacherschließung
lokal Obesity
lokal Diet
lokal Mouse models
lokal Body weight
lokal Leptin
lokal Fats
lokal Food consumption
lokal Food
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. http://orcid.org/0000-0001-9965-6648|https://frl.publisso.de/adhoc/creator/U2llbXMsIFdvbGYtRWJlcmhhcmQ=|https://frl.publisso.de/adhoc/creator/S2x1Z2UsIFJlaW5oYXJ0|https://frl.publisso.de/adhoc/creator/R2VtYmFyZHQsIEZsb3JpYW4=|https://frl.publisso.de/adhoc/creator/U2NodWx0aGVpc3MsIEhlaW56LVBldGVy|https://frl.publisso.de/adhoc/creator/U2NoaXJuZXIsIE1pY2hhZWw=|https://frl.publisso.de/adhoc/creator/V2FsdGhlcizCoFRob21hcw==
1000 Förderer
  1. Deutsche Forschungsgemeinschaft (DFG) |
1000 Fördernummer
  1. SI-483/8/1-2 and -3; WA1441/18/1-2 and -3
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft (DFG) |
    1000 Förderprogramm -
    1000 Fördernummer SI-483/8/1-2 and -3; WA1441/18/1-2 and -3
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6402700.rdf
1000 Erstellt am 2017-06-01T07:40:46.403+0200
1000 Erstellt von 25
1000 beschreibt frl:6402700
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Thu Mar 08 09:49:06 CET 2018
1000 Objekt bearb. Thu Mar 08 09:49:05 CET 2018
1000 Vgl. frl:6402700
1000 Oai Id
  1. oai:frl.publisso.de:frl:6402700 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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