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Sachs, S. ; Götz, A. ; Finan, B.* ; Feuchtinger, A. ; DiMarchi, R.D.* ; Döring, Y.* ; Weber, C.* ; Tschöp, M.H. ; Müller, T.D. ; Hofmann, S.M.

GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease.

Cardiovasc. Diabetol. 22:217 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Agonism at the receptor for the glucose-dependent insulinotropic polypeptide (GIPR) is a key component of the novel unimolecular GIPR:GLP-1R co-agonists, which are among the most promising drugs in clinical development for the treatment of obesity and type 2 diabetes. The therapeutic effect of chronic GIPR agonism to treat dyslipidemia and thus to reduce the cardiovascular disease risk independently of body weight loss has not been explored yet. METHODS: After 8 weeks on western diet, LDL receptor knockout (LDLR-/-) male mice were treated with daily subcutaneous injections of long-acting acylated GIP analog (acyl-GIP; 10nmol/kg body weight) for 28 days. Body weight, food intake, whole-body composition were monitored throughout the study. Fasting blood glucose and intraperitoneal glucose tolerance test (ipGTT) were determined on day 21 of the study. Circulating lipid levels, lipoprotein profiles and atherosclerotic lesion size was assessed at the end of the study. Acyl-GIP effects on fat depots were determined by histology and transcriptomics. RESULTS: Herein we found that treatment with acyl-GIP reduced dyslipidemia and atherogenesis in male LDLR-/- mice. Acyl-GIP administration resulted in smaller adipocytes within the inguinal fat depot and RNAseq analysis of the latter revealed that acyl-GIP may improve dyslipidemia by directly modulating lipid metabolism in this fat depot. CONCLUSIONS: This study identified an unanticipated efficacy of chronic GIPR agonism to improve dyslipidemia and cardiovascular disease independently of body weight loss, indicating that treatment with acyl-GIP may be a novel approach to alleviate cardiometabolic disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Atherosclerosis ; Cardiometabolic Disease ; Dyslipidemia ; Gip Agonist ; Mice ; Obesity ; Acyl-gip; Dependent Insulinotropic Polypeptide; Gastric-inhibitory Polypeptide; Adipose-tissue; Density-lipoprotein
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 1475-2840
e-ISSN 1475-2840
Quellenangaben Band: 22, Heft: 1, Seiten: , Artikelnummer: 217 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Begutachtungsstatus Peer reviewed
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e) G-502390-001
G-501900-221
G-500390-001
G-502200-001
Scopus ID 85168269644
PubMed ID 37592302
Erfassungsdatum 2023-10-06