Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
James A. Haley Veterans' Hospital, Tampa, FL 33612, USA.
Cells. 2022 Aug 22;11(16):2614. doi: 10.3390/cells11162614.
Obesity is of concern to the population because it is known to cause inflammation and oxidative stress throughout the body, leading to patient predisposition for health conditions such as diabetes, hypertension, and some cancers. However, some proteins that are activated in times of oxidative stress may provide cytoprotective properties. In this study, we aim to gain further understanding of the interconnection between Nrf2 and Sesn2 during obesity-related stress and how this relationship can play a role in cardio-protection. Cardiomyocyte-specific Sesn2 knockout (cSesn2) and Sesn2 overexpressed (tTa-tet-Sesn2) mice and their wildtype littermates (Sesn2 and tet-Sesn2, respectively) were assigned to either a normal chow (NC) or a high-fat (HF) diet to induce obesity. After 16 weeks of dietary intervention, heart function was evaluated via echocardiography and cardiac tissue was collected for analysis. Immunoblotting, histology, and ROS staining were completed. Human heart samples were obtained via the LifeLink Foundation and were also subjected to analysis. Overall, these results indicated that the overexpression of Sesn2 appears to have cardio-protective effects on the obese heart through the reduction of ROS and fibrosis present in the tissues and in cardiac function. These results were consistent for both mouse and human heart samples. In human samples, there was an increase in Sesn2 and Nrf2 expression in the obese patients' LV tissue. However, there was no observable pattern of Sesn2/Nrf2 expression in mouse LV tissue samples. Further investigation into the link between the Sesn2/Nrf2 pathway and obesity-related oxidative stress is needed.
肥胖是一个令公众关注的问题，因为它已知会在全身引起炎症和氧化应激，导致患者易患糖尿病、高血压和某些癌症等健康状况。然而，在氧化应激时被激活的一些蛋白质可能提供细胞保护特性。在这项研究中，我们旨在进一步了解 Nrf2 和 Sesn2 之间在肥胖相关应激中的相互关系，以及这种关系如何在心脏保护中发挥作用。心肌细胞特异性 Sesn2 敲除（cSesn2）和 Sesn2 过表达（tTa-tet-Sesn2）小鼠及其野生型同窝仔（分别为 Sesn2 和 tet-Sesn2）被分配到正常饮食（NC）或高脂肪（HF）饮食中以诱导肥胖。在饮食干预 16 周后，通过超声心动图评估心脏功能，并收集心脏组织进行分析。完成了免疫印迹、组织学和 ROS 染色。通过 LifeLink 基金会获得了人类心脏样本，并对其进行了分析。总的来说，这些结果表明 Sesn2 的过表达似乎通过减少组织和心脏功能中的 ROS 和纤维化对肥胖心脏具有心脏保护作用。这些结果在小鼠和人类心脏样本中都是一致的。在人类样本中，肥胖患者的 LV 组织中 Sesn2 和 Nrf2 的表达增加。然而，在小鼠 LV 组织样本中没有观察到 Sesn2/Nrf2 表达的模式。需要进一步研究 Sesn2/Nrf2 途径与肥胖相关氧化应激之间的联系。
