Impaired substrate‐mediated cardiac mitochondrial complex I respiration with unaltered regulation of fatty acid metabolism and oxidative stress status in type 2 diabetic Asian Indians. Issue 7 (6th April 2020) - Jayakumari, Nandini R.
Abstract: Background: The cardiovascular complications associated with type 2 diabetes mellitus could be attributed to changes in myocardial mitochondrial metabolism. Though it is a known fact that permeabilized cardiac muscle fibers and isolated mitochondria are metabolically compromised in the Caucasian population, studies of Asian Indian myocardial mitochondrial function are lacking. Thus, the objective of the present study is to analyze if there is altered cardiac mitochondrial substrate utilization in diabetic Asian Indians. Methods: Mitochondrial substrate utilization was measured using high‐resolution respirometry in isolated mitochondria prepared from right atrial appendage tissues of diabetic and nondiabetic subjects undergoing coronary artery bypass graft surgery. Western blotting and densitometric analysis were also done to compare the levels of proteins involved in fatty acid metabolism and regulation. Results: The mitochondrial oxygen consumption rate for fatty acid substrate was shown to be decreased in diabetic subjects compared to nondiabetic subjects along with an unvaried mitochondrial DNA copy number and uniform levels of electron transport chain complex proteins and proteins involved in fatty acid metabolism and regulation. Decreased glutamate but unchanged pyruvate‐mediated state 3 respiration were also observed in diabetic subjects. Conclusion: The current study reports deranged cardiac mitochondrial fatty acid‐mediated complex I respiration in type 2 diabetic Asian Indians with comparable levels of regulators of fatty acid oxidation to that of nondiabetic myocardium. Altered glutamate‐mediated mitochondrial respiration also points toward possible alterations in mitochondrial complex I activity. When compared with previous reports on other ethnic populations, the current study suggests that Asian Indian population too have altered cardiac mitochondrial substrate utilization. Abstract : Highlights Diabetic myocardium in Asian Indians showed decreased cardiac mitochondrial complex I respiration unaltered mitochondrial DNA copy number unaffected regulation of fatty acid metabolism similar levels of sirtuins and acetylated acyl‐CoA dehydrogenase lack of increased oxidative stress 摘要: 背景: 2型糖尿病心血管并发症可能与心肌线粒体代谢改变有关。虽然在白种人群中通透性心肌纤维和分离的线粒体在代谢上受到损害是众所周知的事实, 但对亚裔印度人心肌线粒体功能的研究还很缺乏。因此, 本研究旨在分析在糖尿病亚裔印度人中是否存在心肌线粒体底物利用率的改变。 方法: 采用高分辨率呼吸计量仪, 测定糖尿病和非糖尿病冠脉搭桥术患者的右心耳分离的线粒体底物利用率。蛋白免疫印迹和密度分析也被用来比较脂肪酸代谢和调节相关的蛋白质水平。 结果: 糖尿病患者与非糖尿病患者相比, 线粒体脂肪酸底物耗氧率降低, 线粒体DNA拷贝数相同, 电子传递链复合物蛋白和脂肪酸代谢调节蛋白水平一致。在糖尿病患者中也观察到谷氨酸减少, 但丙酮酸介导的状态三呼吸速率不变。 结论: 本研究报告了在2型糖尿病亚裔印度人中, 脂肪酸介导的心肌线粒体复合体I呼吸紊乱, 而脂肪酸氧化调节水平则与非糖尿病人群的心肌相当。改变谷氨酸介导的线粒体呼吸也可能导致线粒体复合物I活性的改变。与以前其他种族群体的报告相比, 目前的研究表明亚洲印度群体心肌线粒体底物的利用也发生了改变。