ArticleCardiovascular diabetology2023
GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease.
Article in Cardiovascular diabetology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Association of bodyweight loss with changes in lipids, blood pressure, and fasting serum glucose following tirzepatide treatment in Japanese participants with type 2 diabetes: A post hoc analysis of the SURPASS J-mono trial.Journal of diabetes investigation · 2025Trial
- Emerging role of GLP-1 mono, dual, and triple agonists in the management of MASH-related fibrosis.Cell reports. Medicine · 2026Review
- Tirzepatide as a multi-organ integrator in metabolic diseases: a review of molecular mechanisms and clinical translation.Endocrine · 2026Review
- Revitalizing GIP: Therapeutic Potential in Metabolic and Neurodegenerative Disorders.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Integrative gene-metabolite network analysis of GLP-1 receptor agonists and related incretin pathways in cardiometabolic health.NPJ systems biology and applications · 2025Article
- Genome-wide interaction study with body mass index identifies CYP7A1 and GIPR as genetic modulators of metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2025Article
- Article
- Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte-myofibroblast transition in epidural fibrosis.NPJ Regenerative medicine · 2024Article
- GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells.Cellular and molecular life sciences : CMLS · 2024Article
- Correction: GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease.Cardiovascular diabetology · 2024Article
- Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024Review
- Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program.Cardiovascular diabetology · 2024Article
- Bile acids and incretins as modulators of obesity-associated atherosclerosis.Frontiers in cardiovascular medicine · 2024Review
- The chylomicron saga: time to focus on postprandial metabolism.Frontiers in endocrinology · 2023Review
- Comparative effectiveness of tirzepatide and DPP-4 inhibitors in type 2 diabetes with heart failure.Diabetes & vascular disease researchArticle
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAgonism 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.
methodsAfter 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.
resultsHerein 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.
conclusionsThis 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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.