Polar lipid derangements in type 2 diabetes mellitus: potential pathological relevance of fatty acyl heterogeneity in sphingolipids
Polar lipid derangements in type 2 diabetes mellitus: potential pathological relevance of fatty acyl heterogeneity in sphingolipids
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DOI：
10.1007/s11306-013-0494-0
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发表时间：
2013-01
期刊：
影响因子：
3.6
通讯作者：
G. Shui;S. Lam;J. Stebbins;J. Kusunoki;Xinrui Duan;Bowen Li;W. Cheong;D. Soon;R. Kelly;M. Wenk
中科院分区：
文献类型：
--
作者：
G. Shui;S. Lam;J. Stebbins;J. Kusunoki;Xinrui Duan;Bowen Li;W. Cheong;D. Soon;R. Kelly;M. Wenk
虽然2型糖尿病（T2 DM）患者血浆中性脂质的病理学变化已得到相对充分的表征，但关于该疾病的总体极性脂质组（甘油磷脂和鞘脂）变化的信息有限。为了系统地识别与早期T2 DM相关的极性脂质畸变，我们定量分析并比较了来自不同T2 DM患者组与明显健康对照组的300多种血浆脂质的变化。在轻度T2 DM中，神经酰胺、鞘磷脂、乳糖神经酰胺（LacCer）和神经节苷脂GM 3（GM 3）等鞘脂类显著升高，同时葡萄糖神经酰胺（GluCer）降低，表明轻度糖尿病中GluCer向LacCer的转化增加。根据其酰基链长度，T2 DM中的单个GM 3物质发生改变。T2 DM患者的长链GM 3（脂肪酰碳数≥18）显著增加，而GM 3 18：1/16：0则相反。重要的是，长链GM 3种类与HOMA 2-%β呈负相关，与FBG呈正相关;并且可以区分具有相似HOMA 2-%β的健康个体和轻度糖尿病患者。因此，本研究将鞘脂途径的代谢改变确定为T2 DM发病机制的早期事件，并为旨在确定T2 DM早期分子标志物的更大规模临床研究提供了相关的假设生成新见解。
While pathological alterations in plasma neutral lipids with type 2 diabetes mellitus (T2DM) has been relatively well-characterized, only limited information is available on the variations in global polar lipidome (glycerophospholipids and sphingolipids) with the disease. To systematically identify polar lipid aberrations associated with early stage T2DM, we quantitatively profiled and compared changes in more than 300 plasma lipid species from distinct groups of T2DM patients against overtly healthy controls. Sphingolipid classes including ceramides, sphingomyelins, lactosylceramides (LacCer) and ganglioside GM3 (GM3) were significantly elevated in mild T2DM with a concomitant decrease in glucosylceramides (GluCer), suggesting the increased conversion of GluCer to LacCer in mild diabetes. Individual GM3 species were altered in T2DM according to their acyl chain lengths. While long-chain GM3s (fatty acyl carbon ≥18) were significantly increased in T2DM, the opposite was observed for GM3 18:1/16:0. Importantly, long-chain GM3 species were negatively correlated with HOMA2-%β and positively correlated with FBG; and could distinguish between healthy individuals and mildly diabetic patients with similar HOMA2-%β. The current study therefore identifies metabolic alterations in sphingolipid pathways as early events in T2DM pathogenesis, and provides hypothesis-generating new insights relevant for larger scale clinical studies aimed at identification of early molecular markers of T2DM.