GLP-1R/GIPR Dual Agonism on Gut Lipid Handling
Date
2025
Authors
Tabatabaeian, Farnoosh
Wang, Rita
Mukherjee, Kundanika
Minier, Ethan
Xiao, Changting
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Poster Presentation
Degree Level
Abstract
GLP-1R/GIPR Dual Agonism on Gut Lipid Handling Metabolic diseases (e.g., obesity and type 2 diabetes) are associated with atherogenic dyslipidemia, a condition with high levels of harmful blood lipids causing atherosclerotic cardiovascular disease (ASCVD) and death. The gut mismanages lipids in metabolic diseases by generating excess harmful lipid particles known as chylomicrons. Tirzepatide is a peptide that simultaneously activates the glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). It is an effective treatment for obesity and type 2 diabetes. It has also shown benefits in lipid metabolism and ASCVD risk reduction; however, whether these effects result from weight loss, systemic metabolic changes, or direct modulation of gut lipid handling remains unclear. This study investigates the direct effects of tirzepatide on gut lipid metabolism. We assessed tirzepatide’s effects on gut lipid secretion and metabolic regulation using a rat model. Male Sprague-Dawley rats were fed a high-fat diet or a control diet for 8 weeks and received tirzepatide or placebo injections in the final week. Intraperitoneal glucose tolerance tests (IPGTT) were performed at week 6. Rats were surgically implanted with catheters for lipid infusion and mesenteric lymph collection. We measured body weight, energy intake, lymph flow rate, and triglycerides. Preliminary results suggest that high-fat feeding increases gut lipid output, which is attenuated by tirzepatide. Underlying mechanisms are being investigated via gut morphology and gene expression (qPCR, spatial transcriptomics). These findings provide insights into gut lipid metabolism regulation and potential therapeutic targets for dyslipidemia and ASCVD.
Description
Keywords
Dual GIP and GLP-1 receptor agonist, Metabolic disease, Obesity, Type 2 diabetes, Dyslipidemia, Atherosclerotic cardiovascular disease, Lipid metabolism, Triglycerides, Gut