Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model.
Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model.
复制标题
DOI：
10.1186/s13098-021-00755-z
复制
发表时间：
2021-11-20
影响因子：
4.8
通讯作者：
Tsutsumi YM
中科院分区：
文献类型：
--
作者：
Morio A;Tsutsumi R;Satomi S;Kondo T;Miyoshi H;Kato T;Kuroda M;Kitamura T;Hara K;Saeki N;Sakaue H;Tsutsumi YM
冠状动脉疾病是糖尿病患者发病和死亡的主要原因。以前，我们证明支链氨基酸（BCAA）对心脏缺血/再灌注（I/R）损伤具有心脏保护作用。最近的一项研究表明，亮氨酸（Leu）是一种支链氨基酸，是参与哺乳动物雷帕霉素靶蛋白（mTOR）活性和线粒体功能的关键氨基酸。然而，Leu是否对糖尿病心脏具有心脏保护作用尚不清楚。本研究旨在探讨亮氨酸对高脂饮食诱导的肥胖小鼠糖尿病前期心脏的预适应作用。将I/R损伤的体内小鼠模型分为以下组：对照组、mTOR+/−组和高脂饮食（HFD）诱导的肥胖组。将小鼠随机施用Leu、mTOR抑制剂雷帕霉素（Rap）或Leu与Rap。分离的大鼠心肌细胞进行模拟I/R损伤。进行生化和线粒体功能测定以评估Leu处理引起的mTOR活性和线粒体动力学的变化。与对照组相比，Leu处理的小鼠显示出梗死面积的显著减小（34.8% ± 3.8%对43.1% ± 2.4%，n = 7，p < 0.05），而Rap处理的小鼠没有显示出Leu的保护作用。Leu的这种预处理作用在mTOR+/−小鼠中减弱。此外，Leu增加了融合的线粒体的百分比和线粒体体积，并减少了每个细胞中的线粒体数量。在HFD诱导的肥胖小鼠中，Leu治疗显著降低了梗死面积（41.0% ± 1.1%对51.0% ± 1.4%，n = 7，p < 0.05），这不是由缺血预处理诱导的，并且这种作用被Rap抑制。此外，我们在HFD诱导的肥胖小鼠中观察到Leu治疗增强的mTOR蛋白表达和线粒体融合以及减少的活性氧产生，但在mTOR+/−小鼠中没有。Leu治疗通过促进mTOR活性和线粒体融合改善糖尿病前期小鼠心肌I/R损伤引起的损害。
Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− mice. Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice.
登录
查看更多内容
DOI：
10.3390/antiox6020033
发表时间：
2017-05-17
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Nagdas S;Kashatus DF
通讯作者：
Kashatus DF
影响因子：
16.2
作者：
Stevens, R;Coleman, RL;Holman, RR
通讯作者：
Holman, RR
影响因子：
9.3
作者：
Ding M;Lei J;Han H;Li W;Qu Y;Fu E;Fu F;Wang X
通讯作者：
Wang X
影响因子：
4
作者：
Stary CM;Tsutsumi YM;Patel PM;Head BP;Patel HH;Roth DM
通讯作者：
Roth DM
影响因子：
9.3
作者：
Engbersen, Richard;Riksen, Niels P.;Smits, Paul
通讯作者：
Smits, Paul