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

Research output: Contribution to journalJournal articlepeer-review

Documents

  • dom.14215

    Final published version, 3.27 MB, PDF document

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.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Volume23
Issue number1
Pages (from-to)195-207
Number of pages13
ISSN1462-8902
DOIs
Publication statusPublished - 2020

Bibliographical note

CURIS 2021 NEXS 004

    Research areas

  • bariatric surgery, combinatorial pharmacology, incretins, obesity, plasma proteomics, RECEPTOR AGONIST, BIOMARKERS, DISEASE, HOMEOSTASIS, EXPRESSION, C57BL/6J, GIP

Number of downloads are based on statistics from Google Scholar and www.ku.dk


No data available

ID: 251578807