Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes.

Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes.
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DOI:
10.1371/journal.pone.0041456
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Bruce CR
Bruce CR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Barber MN;Risis S;Yang C;Meikle PJ;Staples M;Febbraio MA;Bruce CR

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肥胖和2型糖尿病(T2 DM)与循环中游离脂肪酸和三酰甘油的增加有关。然而,人们对与这些疾病相关的特定分子脂质种类知之甚少。为了进一步了解这一点,我们对肥胖和胰岛素抵抗的啮齿动物模型以及患有T2 DM的瘦人、肥胖者和肥胖者进行了血浆脂组学分析。用液相色谱-质谱仪进行的脂组分析显示,高脂喂养12周的小鼠血浆中有明显的变化。尽管一些三酰甘油和二酰甘油种类与一些鞘磷脂一起升高,但一个特别有趣的发现是高脂饮食(HFD)诱导的溶血磷脂酰胆碱(LPC)水平降低。由于肝脏、骨骼肌和脂肪组织在新陈代谢中起着重要作用,我们接下来确定HFD是否改变了这些组织中的LPCS。与我们在血浆中的发现相反,只注意到组织LPCS的非常轻微的变化。为了确定血浆LPCS在HFD后何时发生变化,研究了HFD后1、3和6周的小鼠。HFD导致血浆LPCS迅速变化,大多数变化发生在第一周内。与我们的啮齿动物模型一致,来自我们的小型人类队列的数据显示,肥胖者和患有T2 DM的肥胖者的LPC物种数量减少。有趣的是,在肥胖的其他健康个体和肥胖的T2 DM患者之间没有发现差异。与物种无关,我们的脂类图谱显示肥胖状态下循环中的LPC物种普遍减少。此外,我们的数据表明,饮食和肥胖,而不是胰岛素抵抗或糖尿病本身,在改变血浆LPC谱方面起着重要作用。
Obesity and type 2 diabetes (T2DM) are associated with increased circulating free fatty acids and triacylglycerols. However, very little is known about specific molecular lipid species associated with these diseases. In order to gain further insight into this, we performed plasma lipidomic analysis in a rodent model of obesity and insulin resistance as well as in lean, obese and obese individuals with T2DM. Lipidomic analysis using liquid chromatography coupled to mass spectrometry revealed marked changes in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol and diacylglycerol species were elevated along with of a number of sphingolipids, a particularly interesting finding was the high fat diet (HFD)-induced reduction in lysophosphatidylcholine (LPC) levels. As liver, skeletal muscle and adipose tissue play an important role in metabolism, we next determined whether the HFD altered LPCs in these tissues. In contrast to our findings in plasma, only very modest changes in tissue LPCs were noted. To determine when the change in plasma LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring within the first week. Consistent with our rodent model, data from our small human cohort showed a reduction in a number of LPC species in obese and obese individuals with T2DM. Interestingly, no differences were found between the obese otherwise healthy individuals and the obese T2DM patients. Irrespective of species, our lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity. Moreover, our data indicate that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile.
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