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Jall, S. ; Sachs, S. ; Clemmensen, C. ; Finan, B. ; Neff, F. ; DiMarchi, R.D.* ; Tschöp, M.H. ; Müller, T.D. ; Hofmann, S.M.

Monomeric GLP-1/GIP/glucagon triagonism corrects obesity, hepatosteatosis, and dyslipidemia in female mice.

Mol. Metab. 6, 440-446 (2017)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
Objective: Obesity is a major health threat that affects men and women equally. Despite this fact, weight-loss potential of pharmacotherapies is typically first evaluated in male mouse models of diet-induced obesity (DIO). To address this disparity we herein determined whether a monomeric peptide with agonism at the receptors for glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon is equally efficient in correcting DIO, dyslipidemia, and glucose metabolism in DIO female mice as it has been previously established for DIO male mice. Methods: Female C57BL/6J mice and a cohort of fatmass-matched C57BL/6J male mice were treated for 27 days via subcutaneous injections with either the GLP-1/GIP/glucagon triagonist or PBS. A second cohort of C57BL/6J male mice was included to match the females in the duration of the high-fat, high-sugar diet (HFD) exposure. Results: Our results show that GLP-1/GIP/glucagon triple agonism inhibits food intake and decreases body weight and body fat mass with comparable potency in male and female mice that have been matched for body fat mass. Treatment improved dyslipidemia in both sexes and reversed diet-induced steatohepatitis to a larger extent in female mice compared to male mice. Conclusions: We herein show that a recently developed unimolecular peptide triagonist is equally efficient in both sexes, suggesting that this polypharmaceutical strategy might be a relevant alternative to bariatric surgery for the treatment of obesity and related metabolic disorders.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Diabetes ; Dyslipidemia ; Glucose Homeostasis ; Obesity ; Pharmacotherapy ; Sex Differences; Fatty Liver-disease; Insulin-resistance; Bariatric Surgery; Glucose-tolerance; Body-weight; Life-style; Diet; Sex; Steatohepatitis; Cell
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 6, Heft: 5, Seiten: 440-446 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Pathology (PATH)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30201 - Metabolic Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) G-502200-001
G-500300-001
G-501900-221
G-502390-001
G-500600-001
DOI 10.1016/j.molmet.2017.02.002
WOS ID WOS:000404855000006
Scopus ID 85014827561
Erfassungsdatum 2017-04-28
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