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)
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
Publication type
Article: Journal article
Document type
Scientific Article
Thesis type
Editors
Keywords
Atherosclerosis ; Cardiometabolic Disease ; Dyslipidemia ; Gip Agonist ; Mice ; Obesity ; Acyl-gip; Dependent Insulinotropic Polypeptide; Gastric-inhibitory Polypeptide; Adipose-tissue; Density-lipoprotein
Keywords plus
Language
english
Publication Year
2023
Prepublished in Year
0
HGF-reported in Year
2023
ISSN (print) / ISBN
1475-2840
e-ISSN
1475-2840
ISBN
Book Volume Title
Conference Title
Conference Date
Conference Location
Proceedings Title
Quellenangaben
Volume: 22,
Issue: 1,
Pages: ,
Article Number: 217
Supplement: ,
Series
Publisher
BioMed Central
Publishing Place
Campus, 4 Crinan St, London N1 9xw, England
Day of Oral Examination
0000-00-00
Advisor
Referee
Examiner
Topic
University
University place
Faculty
Publication date
0000-00-00
Application date
0000-00-00
Patent owner
Further owners
Application country
Patent priority
Reviewing status
Peer reviewed
POF-Topic(s)
30201 - Metabolic Health
90000 - German Center for Diabetes Research
30205 - Bioengineering and Digital Health
Research field(s)
Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP Element(s)
G-502390-001
G-501900-221
G-500390-001
G-502200-001
Grants
Copyright
Erfassungsdatum
2023-10-06