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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

With an increasing prevalence of obesity related kidney disease, exploring the mechanisms of therapeutic method is of critical importance. Empagliflozin is a new antidiabetic agent with broad clinical application prospect in cardiovascular and renal diseases. However, a metabonomics-based renoprotective mechanism of empagliflozin in obesity remains unclear. Our results showed that empagliflozin significantly alleviated the deposition of lipid droplet, glomerular and tubular injury. The innovation lied in detection of empagliflozin-targeted differential metabolites in kidneys. Compared with normal control mice, obese mice showed higher levels of All-trans-heptaprenyl diphosphate, Biliverdin, Galabiose, Galabiosylceramide (d18:1/16:0), Inosine, Methylisocitric acid, Uric acid, Xanthosine, O-glutarylcarnitine, PG(20:3(8Z,11Z,14Z)/0:0), PG(20:4(5Z,8Z,11Z,14Z)/0:0), PE(O-16:0/0:0), PG(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0), and lower level of Adenosine. Empagliflozin regulated these metabolites in the opposite direction. Associated metabolic pathways were Phospholipids metabolism, Purine metabolism, and Biliverdin metabolism. Most of metabolites were associated with inflammatory response and oxidative stress. Empagliflozin improved the oxidative stress and inflammation imbalance. Our study revealed the metabonomics-based renoprotective mechanism of empagliflozin in obese mice for the first time. Empagliflozin may be a promising tool to delay the progression of obesity-related kidney disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Shuchun Chen reports was provided by Department of Endocrinology, Hebei General Hospital. Shuchun Chen reports a relationship with Department of Endocrinology, Hebei General Hospital that includes: non-financial support. No funding was received for conducting this study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Obesity is a risk factor for cardiovascular disease, leading to ventricular dysfunction and cardiac fibrosis, in which non-cardiomyocytes (nonCMs) play an important role. Early detection and treatment of heart illness may help to limit its progression. We screened for key markers of obesity-induced cardiac fibrosis using single-cell transcriptomics techniques. To begin, an obese mouse model was constructed using a high-fat diet. From a pathogenic perspective, pathological alterations in the obesity-induced heart were found. Differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed. Then, to look for hub genes, key modules of DEGs were built. Finally, the cellular location of the hub genes was investigated. In mice, a high-fat diet raised body weight, messed up myocardial shape, and increased cardiac collagen content. NonCMs transcriptome data revealed 15 different cell types, including fibroblasts, immunological cells, and endothelial cells. There were a total of 33 DEGs found, with 22 up-regulated genes and 11 down-regulated genes. DEGs have a high connection with collagen and extracellular matrix (ECM), according to functional enrichment analysis. Col1a1 and Col1a2 scored well in module analysis and hub gene screening, and were chosen as hub genes. Col1a1 and Col1a2 were shown to be mostly expressed by fibroblasts after localization study. As a result, we believe Col1a1 and Col1a2 may be important markers of obesity-induced cardiac fibrosis, in which fibroblasts play a critical role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)