Targeting on Nrf2/Sesn2 Signaling to Rescue Cardiac Dysfunction during High-Fat Diet-Induced Obesity.
Targeting on Nrf2/Sesn2 Signaling to Rescue Cardiac Dysfunction during High-Fat Diet-Induced Obesity.
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肥胖是人们关注的问题，因为已知它会引起全身炎症和氧化应激，导致患者易患糖尿病、高血压和某些癌症等健康问题。然而，一些在氧化应激时被激活的蛋白质可能提供细胞保护特性。在这项研究中，我们的目标是进一步了解Nrf2和Sesn2在肥胖相关应激过程中的相互联系，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）小鼠及其野生型幼崽（分别为Sesn2flox/flox和tet-Sesn2）被分配到正常食物（NC）或高脂肪（HF）饮食中诱导肥胖。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。完成免疫印迹、组织学和ROS染色。人类心脏样本通过LifeLink基金会获得，并进行了分析。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，肥胖患者左室组织中Sesn2和Nrf2表达增加。然而，Sesn2/Nrf2在小鼠左室组织样本中没有明显的表达模式。需要进一步研究Sesn2/Nrf2通路与肥胖相关氧化应激之间的联系。
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 (Sesn2flox/flox 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.
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影响因子：
20.1
作者：
Ren D;Fedorova J;Davitt K;Van Le TN;Griffin JH;Liaw PC;Esmon CT;Rezaie AR;Li J
通讯作者：
Li J
DOI：
10.1016/j.trsl.2014.05.001
发表时间：
2014-10
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Cavalera M;Wang J;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
39.3
作者：
Badimon, Lina;Bugiardini, Raffaele;Koller, Akos
通讯作者：
Koller, Akos
影响因子：
4.6
作者：
Verdile G;Keane KN;Cruzat VF;Medic S;Sabale M;Rowles J;Wijesekara N;Martins RN;Fraser PE;Newsholme P
通讯作者：
Newsholme P
DOI：
10.1016/b978-0-12-803269-5.00002-4
发表时间：
2016-01-01
期刊：
OXIDATIVE STRESS AND BIOMATERIALS
影响因子：
--
作者：
Chatterjee, Shampa
通讯作者：
Chatterjee, Shampa