PuSH - Publication Server of Helmholtz Zentrum München: Long-acting neurotensin synergizes with liraglutide to reverse obesity through a melanocortin-dependent pathway.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Ratner, C.* ; He, Z.* ; Grunddal, K.V.* ; Skov, L.J.* ; Hartmann, B.* ; Zhang, F.* ; Feuchtinger, A. ; Bjerregaard, A.* ; Christoffersen, C.* ; Tschöp, M.H. ; Finan, B.* ; DiMarchi, R.D.* ; Leinninger, G.M.* ; Williams, K.W.* ; Clemmensen, C.* ; Holst, B.*

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

Diabetes 68, 1329-1340 (2019)

Publ. Version/Full Text

Postprint

Research data

DOI

PMC

	Open Access Green

Abstract
Metrics
Extra information

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 syner-gized 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.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Glp-1 Receptor Agonist; Diet-induced Obese; Food-intake; Administered Neurotensin; Glucose-homeostasis; Peptide-1 Receptor; Corrects Obesity; Pomc Neurons; Leptin; Thermogenesis

ISSN (print) / ISBN 0012-1797

e-ISSN 1939-327X

Journal Diabetes

Quellenangaben Volume: 68, Issue: 6, Pages: 1329-1340

Publisher American Diabetes Association

Publishing Place Alexandria, VA.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Analytical Pathology (AAP)
Institute of Diabetes and Obesity (IDO)