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

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Harvard

Sachs, S, Niu, L, Geyer, P, Jall, S, Kleinert, M, Feuchtinger, A, Stemmer, K, Brielmeier, M, Finan, B, DiMarchi, RD, Tschöp, MH, Wewer Albrechtsen, N, Mann, M, Müller, TD & Hofmann, SM 2021, 'Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice', Diabetes, Obesity and Metabolism, bind 23, nr. 1, s. 195-207. https://doi.org/10.1111/dom.14215

APA

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. (2021). Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice. Diabetes, Obesity and Metabolism, 23(1), 195-207. https://doi.org/10.1111/dom.14215

CBE

Sachs S, Niu L, Geyer P, Jall S, Kleinert M, Feuchtinger A, Stemmer K, Brielmeier M, Finan B, DiMarchi RD, Tschöp MH, Wewer Albrechtsen N, Mann M, Müller TD, Hofmann SM. 2021. Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice. Diabetes, Obesity and Metabolism. 23(1):195-207. https://doi.org/10.1111/dom.14215

MLA

Vancouver

Author

Sachs, Stephan ; Niu, Lili ; Geyer, Philipp ; Jall, Sigrid ; Kleinert, Maximilian ; Feuchtinger, Annette ; Stemmer, Kerstin ; Brielmeier, Markus ; Finan, Brian ; DiMarchi, Richard D ; Tschöp, Matthias H ; Wewer Albrechtsen, Nicolai ; Mann, Matthias ; Müller, Timo D ; Hofmann, Susanna M. / Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice. I: Diabetes, Obesity and Metabolism. 2021 ; Bind 23, Nr. 1. s. 195-207.

Bibtex

@article{f50e7608397a441d8b3fde9fe0b266d6,
title = "Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice",
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.",
keywords = "bariatric surgery, combinatorial pharmacology, incretins, obesity, plasma proteomics",
author = "Stephan Sachs and Lili Niu and Philipp Geyer and Sigrid Jall and Maximilian Kleinert and Annette Feuchtinger and Kerstin Stemmer and Markus Brielmeier and Brian Finan and DiMarchi, {Richard D} and Tsch{\"o}p, {Matthias H} and {Wewer Albrechtsen}, Nicolai and Matthias Mann and M{\"u}ller, {Timo D} and Hofmann, {Susanna M}",
note = "{\textcopyright} 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.",
year = "2021",
month = jan,
doi = "10.1111/dom.14215",
language = "English",
volume = "23",
pages = "195--207",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Plasma proteome profiles treatment efficacy of incretin dual agonism in diet-induced obese female and male mice

AU - Sachs, Stephan

AU - Niu, Lili

AU - Geyer, Philipp

AU - Jall, Sigrid

AU - Kleinert, Maximilian

AU - Feuchtinger, Annette

AU - Stemmer, Kerstin

AU - Brielmeier, Markus

AU - Finan, Brian

AU - DiMarchi, Richard D

AU - Tschöp, Matthias H

AU - Wewer Albrechtsen, Nicolai

AU - Mann, Matthias

AU - Müller, Timo D

AU - Hofmann, Susanna M

N1 - © 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

KW - bariatric surgery

KW - combinatorial pharmacology

KW - incretins

KW - obesity

KW - plasma proteomics

UR - http://www.scopus.com/inward/record.url?scp=85096748630&partnerID=8YFLogxK

U2 - 10.1111/dom.14215

DO - 10.1111/dom.14215

M3 - Journal article

C2 - 33001570

VL - 23

SP - 195

EP - 207

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 1

ER -

ID: 61760940