Myocardium of type 2 diabetic and obese patients is characterized by alterations in sphingolipid metabolic enzymes but not by accumulation of ceramide
Myocardium of type 2 diabetic and obese patients is characterized by alterations in sphingolipid metabolic enzymes but not by accumulation of ceramide
复制标题
DOI：
10.1194/jlr.m900002-jlr200
复制
发表时间：
2010-01-01
影响因子：
6.5
通讯作者：
Gorski, Jan
中科院分区：
文献类型：
--
作者：
Baranowski, Marcin;Blachnio-Zabielska, Agnieszka;Gorski, Jan
来自动物实验的数据强烈表明，神经酰胺是心脏中脂毒性的重要介质，并且神经酰胺的积累有助于与2型糖尿病和肥胖相关的心肌细胞凋亡。然而，目前还不清楚类似的关系是否也存在于人类的心脏。因此，我们的目的是研究肥胖和2型糖尿病患者的心肌细胞凋亡是否与神经酰胺水平升高有关。该研究包括11名无2型糖尿病史（n = 11，OWT）或有2型糖尿病史（n = 15，T2 D-OWT）的瘦型和26名超重或中度肥胖受试者。在冠状动脉搭桥手术时从患者中获得右心耳样本。与瘦型受试者相比，OWT患者心肌中的DNA片段化程度（细胞凋亡的标志物）显著更高，T2 D-OWT受试者中的DNA片段化程度进一步增加。但神经酰胺和鞘氨醇碱的含量保持稳定。有趣的是，与瘦型受试者相比，OWT和T2 D-OWT患者心肌中参与神经酰胺合成和降解的酶（包括丝氨酸棕榈酰转移酶、鞘氨醇激酶1、中性鞘磷脂酶和神经酰胺酶）的mRNA水平明显较高。我们的研究结果表明，在人类心脏中，或者至少在心房中，神经酰胺不是与肥胖和2型糖尿病相关的心肌细胞凋亡的主要因素。Baranowski，M.，A. Blachnio-Zabielska，T.赫恩勒，D.哈拉修克湾马特拉克，M.克纳普，P. Zabielski和J. Gorski。2型糖尿病和肥胖患者的肌萎缩特征在于鞘脂代谢酶的改变，而不是神经酰胺的积累。J. Lipid Res. 2010. 51：74-80。2009年12月14日，在ISI，Thomson Scientific
Data from animal experiments strongly suggest that ceramide is an important mediator of lipotoxicity in the heart and that accumulation of ceramide contributes to cardiomyocyte apoptosis associated with type 2 diabetes and obesity. However, it remains unknown whether a similar relationship is present also in the human heart. Therefore, we aimed to examine whether myocardial apoptosis in obese and type 2 diabetic patients is associated with elevated ceramide level. The study included 11 lean and 26 overweight or moderately obese subjects without (n = 11, OWT) or with (n = 15, T2D-OWT) a history of type 2 diabetes. Samples of the right atrial appendage were obtained from patients at the time of coronary bypass surgery. Compared with lean subjects, the extent of DNA fragmentation (a marker of apoptosis) was significantly higher in the myocardium of OWT patients and increased further in T2D-OWT subjects. However, the content of ceramide and sphingoid bases remained stable. Interestingly, the mRNA level of enzymes involved in synthesis and degradation of ceramide including serine palmitoyltransferase, sphingosine kinase 1, neutral sphingomyelinase, and ceramidases was markedly higher in the myocardium of OWT and T2D-OWT patients compared with lean subjects. Our results indicate that in the human heart, or at least in the atrium, ceramide is not a major factor in cardiomyocyte apoptosis associated with obesity and type 2 diabetes.-Baranowski, M., A. Blachnio-Zabielska, T. Hirnle, D. Harasiuk, K. Matlak, M. Knapp, P. Zabielski, and J. Gorski. Myocardium of type 2 diabetic and obese patients is characterized by alterations in sphingolipid metabolic enzymes but not by accumulation of ceramide. J. Lipid Res. 2010. 51: 74-80. at ISI, Thomson Scientific on December 14, 2009