Impact of GLP1 activator on perivascular adipose tissue function of ovariectomized obese SHR females

• Grant number: 24/20653-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Tiago Januário da Costa
• Grantee: Maria Clara Teles de Queiroz
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Obesity in postmenopausal women is a risk factor for cardiovascular diseases. While estrogen is an essential hormone in regulating cardiometabolic parameters, especially concerning vascular and adipocyte function, estrogen as hormone therapy remains unsafe for all women. Recently, the use of semaglutide, a GLP-1 receptor agonist, has shown promising results in both weight loss and reduction of adverse cardiovascular events, making it an exciting alternative for postmenopausal women, particularly those for whom estrogen use is not recommended. It is still not well understood how semaglutide may directly affect the vasculature. Among the vascular components that could be targeted is perivascular adipose tissue (PVAT), which directly influences the vasculature by promoting an anticontractile effect through the production of various vasoactive factors. PVAT adopts different phenotypes across the vascular bed and can be classified as white or brown adipose tissue, with characteristics similar to visceral and scapular tissues. The classic anticontractile effect of PVAT is abolished in cardiometabolic diseases, such as obesity and estrogen deficiency (induced by ovariectomy - OVX), due to the increased pro-inflammatory profile. This project hypothesizes that, besides promoting weight loss, semaglutide exerts anti-inflammatory effects on PVAT in overweight OVX models, which would explain its cardiovascular protection. The aim is to identify the protective role of GLP-1 in the PVAT of obese OVX females and investigate the impact of semaglutide on the anti-inflammatory profile. This project will highlight understanding the therapeutic potential of GLP-1 and semaglutide in improving cardiovascular function in overweight postmenopausal women, paving the way for new cardiovascular treatment approaches for this at-risk group. (AU)