Lipid-gene regulatory network reveals coregulations of triacylglycerol with phosphatidylinositol/lysophosphatidylinositol and with hexosyl-ceramide
Lipid-gene regulatory network reveals coregulations of triacylglycerol with phosphatidylinositol/lysophosphatidylinositol and with hexosyl-ceramide
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脂质基因调控网络揭示了三酰甘油与磷脂酰肌醇/溶血磷脂酰肌醇以及己糖基神经酰胺的共调节
DOI：
10.1016/j.bbalip.2018.11.010
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发表时间：
2019
影响因子：
4.8
通讯作者：
Huang Xun
中科院分区：
文献类型：
--
作者：
Wang Wei;Xin Jingxue;Yang Xiao;Lam Sin Man;Shui Guanghou;Wang Yong;Huang Xun
脂质稳态对正常细胞功能的执行和生理条件的维持至关重要。脂质的生物物理特性和复杂的代谢网络是脂质稳态中不同种类脂质的协调调节的基础。为了揭示不同脂质之间的稳态反应，我们通过RNAi系统地敲除了果蝇as2细胞内40个脂质代谢基因，并分析了脂质组学的变化。脂质聚类分析表明，许多基因对以顺序方式或共享相同的底物紧密聚集。通过脂质基因调控网络分析，我们进一步发现，三酰甘油（TAG）的减少与磷脂酰肌醇（PI）和溶磷脂酰肌醇（LPI）的增加或己糖基神经酰胺（HexCer）和羟基己糖基神经酰胺（OH-HexCer）的减少有关。重要的是，在人Hela细胞中也发现了TAG与LPI/PI之间的负共调节，TAG与HexCer之间的正共调节。总之，我们的研究结果揭示了TAG与PI/LPI和HexCer在脂质稳态中的共同调控。
Lipid homeostasis is important for executing normal cellular functions and maintaining physiological conditions. The biophysical properties and intricate metabolic network of lipids underlie the coordinated regulation of different lipid species in lipid homeostasis. To reveal the homeostatic response among different lipids, we systematically knocked down 40 lipid metabolism genes inDrosophilaS2 cells by RNAi and profiled the lipidomic changes. Clustering analyses of lipids reveal that many pairs of genes acting in a sequential fashion or sharing the same substrate are tightly clustered. Through a lipid-gene regulatory network analysis, we further found that a reduction of triacylglycerol (TAG) is associated with an increase of phosphatidylinositol (PI) and lysophosphatidylinositol (LPI) or a reduction of hexosyl-ceramide (HexCer) and hydroxylated hexosyl-ceramide (OH-HexCer). Importantly, negative coregulation between TAG and LPI/PI, and positive coregulation between TAG and HexCer, were also found in human Hela cells. Together, our results reveal coregulations of TAG with PI/LPI and with HexCer in lipid homeostasis.