Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Long-acting neurotensin synergizes with liraglutide to reverse obesity through a Melanocortin-dependent pathway

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Epigenome-wide association study of incident type 2 diabetes in a British population: EPIC-Norfolk study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Lean women with polycystic ovary syndrome and insulin resistance have normal incretin effect, which is unaffected by metformin therapy

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

  3. GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in HNF1A-diabetes

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

  4. Cardiac Autonomic Function is Associated With Myocardial Flow Reserve in Type 1 Diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Validity of biopsy-based drug effects in a diet-induced obese mouse model of biopsy-confirmed NASH

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Galnt11 regulates kidney function by glycosylating the endocytosis receptor megalin to modulate ligand binding

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Apolipoprotein M-bound sphingosine-1-phosphate regulates blood-brain barrier paracellular permeability and transcytosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Apolipoprotein M/sphingosine-1-phosphate: novel effects on lipids, inflammation and kidney biology

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Diurnal regulation of sphingolipids in blood

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Cecilia Ratner
  • Zhenyan He
  • Kaare V Grunddal
  • Louise J Skov
  • Bolette Hartmann
  • Fa Zhang
  • Annette Feuchtinger
  • Anette Bjerregaard
  • Christina Christoffersen
  • Matthias H Tschöp
  • Brian Finan
  • Richard D DiMarchi
  • Gina M Leinninger
  • Kevin W Williams
  • Christoffer Clemmensen
  • Birgitte Holst
Vis graf over relationer

Neurotensin (NT), a gut hormone and neuropeptide, increases in circulation after bariatric surgery in rodents and humans and inhibits food intake in mice. However, its potential to treat obesity and the subsequent metabolic dysfunctions have been difficult to assess owing to its short half-life in vivo. Here, we demonstrate that a long-acting, pegylated analog of the NT peptide (P-NT) reduces food intake, body weight, and adiposity in diet-induced obese mice when administered once daily for 6 days. Strikingly, when P-NT was combined with the glucagon-like peptide 1 mimetic liraglutide, the two peptides synergized to reduce food intake and body weight relative to each monotherapy, without inducing a taste aversion. Further, P-NT and liraglutide coadministration improved glycemia and reduced steatohepatitis. Finally, we show that the melanocortin pathway is central for P-NT-induced anorexia and necessary for the full synergistic effect of P-NT and liraglutide combination therapy. Overall, our data suggest that P-NT and liraglutide combination therapy could be an enhanced treatment for obesity with improved tolerability compared with liraglutide monotherapy.

OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind68
Udgave nummer6
Sider (fra-til)1329-1340
Antal sider12
ISSN0012-1797
DOI
StatusUdgivet - jun. 2019

Bibliografisk note

© 2019 by the American Diabetes Association.

ID: 58287475