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Journal Article

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

MPS-Authors
/persons/resource/persons196483

Geyer,  Philipp
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Wewer Albrechtsen,  Nicolai J.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78356

Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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dom.14215.pdf
(Publisher version), 4MB

Supplementary Material (public)

dom14215-sup-0001-figures1.pdf
(Supplementary material), 5MB

dom14215-sup-0002-tables1.xlsx
(Supplementary material), 399KB

dom14215-sup-0003-tables2.xlsx
(Supplementary material), 17KB

dom14215-sup-0004-tables3.xlsx
(Supplementary material), 41KB

dom14215-sup-0005-tables4.xlsx
(Supplementary material), 94KB

dom14215-sup-0006-tables5.xlsx
(Supplementary material), 95KB

Citation

Sachs, S., Niu, L., Geyer, P., Jall, S., Kleinert, M., Feuchtinger, A., et al. (2021). Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice. Diabetes, Obesity and Metabolism, 23, 195-207. doi:10.1111/dom.14215.


Cite as: http://hdl.handle.net/21.11116/0000-0007-D5C9-6
Abstract
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.