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链脲佐菌素诱导糖尿病大鼠肝磷脂组学特征重塑。

Remodeling of liver phospholipidomic profile in streptozotocin-induced diabetic rats.

机构信息

Mass Spectrometry Center, QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

出版信息

Arch Biochem Biophys. 2013 Oct 15;538(2):95-102. doi: 10.1016/j.abb.2013.07.029. Epub 2013 Aug 13.

Abstract

Lipid homeostasis in liver is known to be altered with diabetes mellitus, ultimately leading to liver damage and related complications. The present work aimed to evaluate changes in the liver phospholipid profile after 4 months of uncontrolled hyperglycemia. Twenty Wistar rats were divided into two groups: control and streptozotocin-treated (T1DM). After 4 months, animals were sacrificed and morphological characterization of liver was performed and related with serum markers of hepatic damage. Lipid extracts were obtained from liver and phospholipid (PL) classes were quantified. Lipid molecular species were determined by LC-MS and LC-MS/MS, and fatty acids by GC-MS. Concomitantly with signs of hepatic damage we found variations in the relative amount of phospholipid classes in T1DM, characterized by a decrease in PLs with choline head group, and by an increase in the relative content of other PL classes. A remodeling in PL fatty acyl chains was observed in T1DM liver, with a similar pattern to all the PL classes, and consisting in the reduction of 16:0 and an increase of 18:0 and 18:2 acyl chains. The observed changes in T1DM lipid profile may contribute to the altered membrane properties underlying hepatic damage, worsening the metabolic alterations that characterize T1DM.

摘要

已知肝脏中的脂质稳态会因糖尿病而改变,最终导致肝损伤和相关并发症。本研究旨在评估未经控制的高血糖症 4 个月后肝脏磷脂谱的变化。将 20 只 Wistar 大鼠分为两组:对照组和链脲佐菌素处理组(T1DM)。4 个月后,处死动物并进行肝脏形态学特征描述,并与肝损伤的血清标志物相关联。从肝脏中提取脂质提取物,并定量磷脂(PL)类。通过 LC-MS 和 LC-MS/MS 测定脂质分子种类,并通过 GC-MS 测定脂肪酸。与肝损伤的迹象同时,我们发现 T1DM 中磷脂类的相对含量发生了变化,其特征是胆碱头部基团的 PL 减少,而其他 PL 类的相对含量增加。在 T1DM 肝脏中观察到 PL 脂肪酸酰链的重塑,所有 PL 类均呈现出相似的模式,表现为 16:0 的减少和 18:0 和 18:2 酰链的增加。T1DM 脂质谱的观察到的变化可能导致肝损伤下膜性质的改变,使 T1DM 特征的代谢改变恶化。

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