Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: A shotgun lipidomics study
Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: A shotgun lipidomics study
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DOI：
10.1021/bi7004015
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发表时间：
2007-05-29
期刊：
影响因子：
2.9
通讯作者：
Gross, Richard W.
中科院分区：
文献类型：
--
作者：
Han, Xianlin;Yang, Jingyue;Gross, Richard W.
最近，我们已经确定了显着的消耗心磷脂（CL）在糖尿病心肌6周后链脲佐菌素（STZ）注射，伴随着三酰甘油含量的增加和极性脂质分子种类的多种变化。然而，在糖尿病状态下6周后，糖尿病心肌病的主要脂质标志各自伴随存在，因此，不可能确定糖尿病心肌中脂质改变的时间过程。使用新开发的增强鸟枪脂质组学方法，我们证明了在糖尿病的最早阶段STZ治疗的心脏中大量CL分子种类的急剧损失，伴随着剩余CL分子种类的深刻重塑，包括18：2-22：6 - 22：6 - 22：6 CL含量增加16倍。CL代谢的这些改变发生在诱导糖尿病状态后的几天内，并在糖尿病心肌中出现三酰甘油蓄积之前。同样，在ob/ob小鼠中，也发现了从含18：2 FA的CL分子种类到含22：6 FA的CL分子种类的急剧和进行性再分布。总的来说，这些结果表明在糖尿病的最早阶段CL水解和重塑的变化，并在糖尿病性心肌病中沉淀线粒体功能障碍的CL含量的变化的作用是一致的。
Recently, we have identified the dramatic depletion of cardiolipin (CL) in diabetic myocardium 6 weeks after streptozotocin (STZ) injection that was accompanied by increases in triacylglycerol content and multiple changes in polar lipid molecular species. However, after 6 weeks in the diabetic state, the predominant lipid hallmarks of diabetic cardiomyopathy were each present concomitantly, and thus, it was impossible to identify the temporal course of lipid alterations in diabetic myocardium. Using the newly developed enhanced shotgun lipidomics approach, we demonstrated the dramatic loss of abundant CL molecular species in STZ-treated hearts at the very earliest stages of diabetes accompanied by a profound remodeling of the remaining CL molecular species including a 16-fold increase in the content of 18:2-22:6-22:6-22:6 CL. These alterations in CL metabolism occur within days after the induction of the diabetic state and precede the triacylglycerol accumulation manifest in diabetic myocardium. Similarly, in ob/ob mice, a dramatic and progressive redistribution from 18:2 FA-containing CL molecular species to 22:6 FA-containing CL molecular species was also identified. Collectively, these results demonstrate alterations in CL hydrolysis and remodeling at the earliest stages of diabetes and are consistent with a role for alterations in CL content in precipitating mitochondrial dysfunction in diabetic cardiomyopathy.