Yue Lin, Wang Yue, Wang Cuiying, Niu Shu, Dong Xihong, Guan Yaqing, Chen Shuchun
Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050000, P.R. China.
Department of Ultrasonography, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050000, P.R. China.
Open Med (Wars). 2024 Aug 20;19(1):20241012. doi: 10.1515/med-2024-1012. eCollection 2024.
Empagliflozin has been shown in clinical studies to lower the risk of adverse cardiovascular events. Using proteomics, the current study aims to determine whether empagliflozin reduces aortic alterations in obese mice and to investigate its molecular mechanism of action.
We constructed obese mice and then treated them with empagliflozin. Changes in the weight of the mice were recorded. Blood glucose and lipid levels were measured in each group of mice, and changes in pulse wave velocity and aortic structure were recorded. In addition, changes in aortic protein expression were detected by proteomics and analyzed bioinformatically.
Proteomics results showed that 507 differentially expressed proteins (DEPs) were identified in the comparison of normal and obese mice, while 90 DEPs were identified in the comparison of obese and empagliflozin-treated mice. Examination of these three groups revealed that DEPs were largely associated with the digestion of unsaturated fats. Among them, empagliflozin significantly reduced the expression of fatty acid synthase (FASN), acyl-CoA desaturase 3 (SCD3), ACSL1. and ACSL5 in the aorta of obesity-induced mice, and there was a close relationship between the four.
Empagliflozin reduced the protein expression of FASN, SCD3, ACSL1, and ACSL5 in the aorta of obese mice and improved aortic fatty acid metabolism and reduced vascular stiffness for vasoprotective effects.
临床研究表明，恩格列净可降低不良心血管事件的风险。本研究旨在利用蛋白质组学确定恩格列净是否能减轻肥胖小鼠的主动脉改变，并探究其分子作用机制。
构建肥胖小鼠模型，然后用恩格列净对其进行治疗。记录小鼠体重变化。测量每组小鼠的血糖和血脂水平，并记录脉搏波速度和主动脉结构的变化。此外，通过蛋白质组学检测主动脉蛋白表达的变化，并进行生物信息学分析。
蛋白质组学结果显示，在正常小鼠与肥胖小鼠的比较中鉴定出507种差异表达蛋白（DEP），而在肥胖小鼠与恩格列净治疗小鼠的比较中鉴定出90种DEP。对这三组的检测表明，DEP主要与不饱和脂肪的消化有关。其中，恩格列净显著降低了肥胖诱导小鼠主动脉中脂肪酸合酶（FASN）、酰基辅酶A去饱和酶3（SCD3）、ACSL1和ACSL5的表达，且这四种蛋白之间存在密切关系。
恩格列净降低了肥胖小鼠主动脉中FASN、SCD3、ACSL1和ACSL5的蛋白表达，改善了主动脉脂肪酸代谢，降低了血管僵硬度，具有血管保护作用。
