Sachs, Stephan; Götz, Anna; Finan, Brian; Feuchtinger, Annette; DiMarchi, Richard D; Döring, Yvonne; Weber, Christian; Tschöp, Matthias H; Müller, Timo D; Hofmann, Susanna M (2023). GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease. Cardiovascular diabetology, 22(1), p. 217. BioMed Central 10.1186/s12933-023-01940-2
|
Text
s12933-023-01940-2.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology |
UniBE Contributor: |
Döring, Yvonne |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1475-2840 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
18 Aug 2023 12:38 |
Last Modified: |
18 Aug 2023 12:47 |
Publisher DOI: |
10.1186/s12933-023-01940-2 |
PubMed ID: |
37592302 |
Uncontrolled Keywords: |
Atherosclerosis Cardiometabolic disease Dyslipidemia GIP agonist Mice Obesity acyl-GIP |
BORIS DOI: |
10.48350/185547 |
URI: |
https://boris.unibe.ch/id/eprint/185547 |
Actions (login required)
 |
Edit item |