Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans
Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans
复制标题
DOI：
10.1073/pnas.1222647110
复制
发表时间：
2013-08-27
影响因子：
11.1
通讯作者：
Gooley, Joshua J.
中科院分区：
文献类型：
--
作者：
Chua, Eric Chern-Pin;Shui, Guanghou;Gooley, Joshua J.
昼夜节律系统调节脂质代谢和脂肪组织功能的每日节律。虽然昼夜节律钟功能的破坏与负性心脏代谢终点有关，但对昼夜节律调节的代谢途径的个体间差异知之甚少。在这里，我们使用基于靶向脂质组学的方法来分析20名健康个体血浆中263种脂质的时间过程。在28小时的跨度内，每4小时收集一次血液，并通过HPLC/MS分析血浆脂质。在受试者中，约13%的脂质代谢产物显示出昼夜节律变化。节律跨越所有代谢物类检查，表明广泛的昼夜节律控制脂质介导的能量储存，运输和信号。然而，被确定为节律的脂质的受试者间一致性仅约为20%，并且脂质节律的时间范围在个体之间相距12小时。因此，健康受试者在不同脂质种类之间的节律的时间和强度上显示出实质性变化。强烈的个体间差异也观察到的节奏的血糖和胰岛素，但不是皮质醇。使用具有迭代特征选择的共识聚类，受试者基于甘油三酯和磷脂酰胆碱子集的节律性强度聚类成不同的组，这表明在一般人群中存在不同的昼夜代谢表型。这些结果对与生物钟紊乱相关的脂质代谢紊乱具有潜在的意义。
The circadian system regulates daily rhythms in lipid metabolism and adipose tissue function. Although disruption of circadian clock function is associated with negative cardiometabolic end points, very little is known about interindividual variation in circadian-regulated metabolic pathways. Here, we used targeted lipidomics-based approaches to profile the time course of 263 lipids in blood plasma in 20 healthy individuals. Over a span of 28 h, blood was collected every 4 h and plasma lipids were analyzed by HPLC/MS. Across subjects, about 13% of lipid metabolites showed circadian variation. Rhythmicity spanned all metabolite classes examined, suggesting widespread circadian control of lipid-mediated energy storage, transport, and signaling. Intersubject agreement for lipids identified as rhythmic was only about 20%, however, and the timing of lipid rhythms ranged up to 12 h apart between individuals. Healthy subjects therefore showed substantial variation in the timing and strength of rhythms across different lipid species. Strong interindividual differences were also observed for rhythms of blood glucose and insulin, but not cortisol. Using consensus clustering with iterative feature selection, subjects clustered into different groups based on strength of rhythmicity for a subset of triglycerides and phosphatidylcholines, suggesting that there are different circadian metabolic phenotypes in the general population. These results have potential implications for lipid metabolism disorders linked to circadian clock disruption.