PuSH - Publication Server of Helmholtz Zentrum München: Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Sachs, S. ; Niu, L.* ; Geyer, P.* ; Jall, S. ; Kleinert, M. ; Feuchtinger, A. ; Stemmer, K. ; Brielmeier, M. ; Finan, B.* ; DiMarchi, R.D.* ; Tschöp, M.H. ; Wewer Albrechtsen, N.* ; Mann, M.* ; Müller, T.D. ; Hofmann, S.M.

Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice.

Diabetes Obes. Metab. 23, 195-207 (2021)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Gold (Paid Option)

Abstract
Metrics
Extra information

Aims Unimolecular peptides targeting the receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) (GLP-1/GIP co-agonist) have been shown to outperform each single peptide in the treatment of obesity and cardiometabolic disease in preclinical and clinical trials. By combining physiological treatment endpoints with plasma proteomic profiling (PPP), we aimed to identify biomarkers to advance non-invasive metabolic monitoring of compound treatment success and exploration of ulterior treatment effects on an individual basis.Materials and methods We performed metabolic phenotyping along with PPP in body weight-matched male and female diet-induced obese (DIO) mice treated for 21 days with phosphate-buffered saline, single GIP and GLP-1 mono-agonists, or a GLP-1/GIP co-agonist.Results GLP-1R/GIPR co-agonism improved obesity, glucose intolerance, non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia with superior efficacy in both male and female mice compared with mono-agonist treatments. PPP revealed broader changes of plasma proteins after GLP-1/GIP co-agonist compared with mono-agonist treatments in both sexes, including established and potential novel biomarkers for systemic inflammation, NAFLD and atherosclerosis. Subtle sex-specific differences have been observed in metabolic phenotyping and PPP.Conclusions We herein show that a recently developed unimolecular GLP-1/GIP co-agonist is more efficient in improving metabolic disease than either mono-agonist in both sexes. PPP led to the identification of a sex-independent protein panel with the potential to monitor non-invasively the treatment efficacies on metabolic function of this clinically advancing GLP-1/GIP co-agonist.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Bariatric Surgery ; Combinatorial Pharmacology ; Incretins ; Obesity ; Plasma Proteomics; Receptor Agonist; Biomarkers; Disease; Homeostasis; Expression; C57bl/6j; Gip

ISSN (print) / ISBN 1462-8902

e-ISSN 1463-1326

Journal Diabetes, Obesity and Metabolism

Quellenangaben Volume: 23, Issue: 1, Pages: 195-207

Publisher Wiley

Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Institute of Diabetes and Obesity (IDO)
Research Unit Analytical Pathology (AAP)
CF Comparative Medicine (CF-Comparative Medicine)

Grants Helmholtz Zentrum Munchen
Deutsche Forschungsgemeinschaft
European Research Council
Helmholtz Alliance ICEMED
Helmholtz cross-program topic "Metabolic Dysfunction"
Helmholtz Initiative on Personalized Medicine iMed
Initiative and Networking Fund of the Helmholtz Association
Research Foundation
Novo Nordisk Foundation
Alexander von Humboldt-Stiftung