Core Viewpoint - The article discusses the recent research findings on the effects of Semaglutide in improving vascular health in obese mice, highlighting its potential as a therapeutic option for obesity-related vascular diseases [6][8][10]. Group 1: Research Findings - A study presented at the 27th Academic Conference of the Chinese Diabetes Society revealed that Semaglutide can significantly improve large vessel stiffness and endothelial permeability abnormalities caused by obesity by inhibiting the p38MAPK/KLF4/Col15a1 signaling pathway [6]. - The research involved 24 mice divided into three groups: normal diet, high-fat diet, and high-fat diet with Semaglutide intervention. Results showed that the Semaglutide group had reduced body weight, blood glucose, insulin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels compared to the high-fat diet group [8]. - The study also utilized proteomics to identify 25 differentially expressed proteins between the normal/high-fat diet groups and the high-fat diet/Semaglutide groups, with a focus on extracellular matrix-related pathways [9]. Group 2: Mechanism of Action - Cell experiments confirmed that palmitic acid activates the p38MAPK signaling pathway, increasing KLF4 expression, which in turn promotes Col15a1 expression. Semaglutide was found to inhibit the p38MAPK pathway, downregulating KLF4 and subsequently reducing Col15a1 expression [10]. - The findings suggest that Semaglutide not only improves metabolic disorders in obese mice but also exhibits significant large vessel protective effects by reducing endothelial permeability and vascular stiffness through the inhibition of the p38MAPK/KLF4/Col15a1 signaling axis [10].