Single-cell transcriptome reveals effects of semaglutide on non-cardiomyocytes of obese mice

• Published in: Biochemical and biophysical research communications Vol. 622; pp. 22 - 29
• Main Authors: Pan, Xiaoyu, Chen, Xing, Ren, Qingjuan, Yue, Lin, Niu, Shu, Li, Zelin, Zhu, Ruiyi, Chen, Xiaoyi, Jia, Zhuoya, Zhen, Ruoxi, Ban, Jiangli, Chen, Shuchun
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 24.09.2022
• Subjects: Cardiac fibrosis; Differentially expressed genes; Fibroblasts; Obesity; Semaglutide; Fibroblasts; Obesity; Cardiac fibrosis; Semaglutide; Differentially expressed genes
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.07.034

Non-cardiomyocytes (nonCMs) play an important part in cardiac fibrosis pathophysiology, but the underlying molecular pathways are unknown. Semaglutide has cardioprotective properties, but it is still unclear whether it helps with cardiac fibrosis and what the processes are. The goal of this study is to use single cell transcriptomics approaches to investigate the molecular mechanism of semaglutide's cardioprotective action in obese mice. We found 15 non-CMs, with fibroblasts making up the majority of them. We found eight DEGs that altered significantly following semaglutide treatment by screening for differentially expressed genes (DEGs). DEGs were shown to have biological activities primarily related to extracellular matrix and collagen synthesis and distribution, with Serpinh1 and Pcolce expression being the most dramatically altered. Serpinh1 and Pcolce were mostly found in fibroblasts, which play a key role in the fibrosis of the heart. Furthermore, we discovered that semaglutide lowered cardiac collagen content and alleviated obesity-induced ventricular wall hypertrophy. As a result, our findings show that Serpinh1 and Pcolce, which are expressed by fibroblasts, may play a role in the development of obese cardiac fibrosis. By reducing Serpinh1 and Pcolce expression and delaying cardiac fibrosis, semaglutide may have a cardioprotective effect. •Obesity can significantly increase cardiac collagen content and ventricular wall thickness.•Semaglutide affects the expression of several genes in non-cardiomyocytes of obese mice.•Obesity is involved in cardiac fibrosis by affecting the expression of Serpinh1 and Pcolce in cardiac fibroblasts.•Semaglutide alleviates cardiac fibrosis by inhibiting the expression of fibroblasts Serpinh1 and Pcolce.