The role of ethanolamine phosphate phospholyase in regulation of astrocyte lipid homeostasis.
The role of ethanolamine phosphate phospholyase in regulation of astrocyte lipid homeostasis.
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DOI：
10.1016/j.jbc.2021.100830
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Wolfgang MJ
中科院分区：
文献类型：
--
作者：
White CJ;Ellis JM;Wolfgang MJ
膳食脂质组成已被证明会影响大脑形态，大脑发育和神经功能。然而，饮食如何独特地调节脑脂质稳态相比，在外周组织的脂质稳态仍然在很大程度上没有特点。为了评估大脑中对饮食变化的脂质反应，我们评估了多种饮食中星形胶质细胞和神经元中的主动翻译mRNA。从这些数据中，乙醇胺磷酸磷脂酶（Etnppl）被确定为星形胶质细胞特异性禁食诱导基因。Etnppl分解代谢磷酸乙醇胺（PEtN），磷酸乙醇胺是磷脂酰乙醇胺（PE）中的一种重要头基前体，也存在于其他类别的神经相关脂质物质中。改变的Etnppl表达以前也与患有情绪障碍的人相关。我们通过在发育过程中表征Etnppl和与PEtN相关基因的共调节以及确定Etnppl损失后对脑脂质组的影响来评估Etnppl在维持脑脂质稳态中的相关性。我们发现Etnppl表达在小鼠早期脑发育的关键窗口期间显著增加，并且也由糖皮质激素诱导。使用Etnppl的组成型敲除（EtnpplKO），我们没有观察到PEtN相关基因表达的强烈变化。然而，Etnppl的损失改变了脑中的磷脂谱，导致脑中PE和PE内的多不饱和脂肪酸和磷脂酰胆碱物质的总丰度增加。总之，这些数据表明，脑磷脂是由酶Etnppl的磷脂酶作用，这是诱导饮食禁食星形胶质细胞。
Dietary lipid composition has been shown to impact brain morphology, brain development, and neurologic function. However, how diet uniquely regulates brain lipid homeostasis compared with lipid homeostasis in peripheral tissues remains largely uncharacterized. To evaluate the lipid response to dietary changes in the brain, we assessed actively translating mRNAs in astrocytes and neurons across multiple diets. From this data, ethanolamine phosphate phospholyase (Etnppl) was identified as an astrocyte-specific fasting-induced gene. Etnppl catabolizes phosphoethanolamine (PEtN), a prominent headgroup precursor in phosphatidylethanolamine (PE) also found in other classes of neurologically relevant lipid species. Altered Etnppl expression has also previously been associated with humans with mood disorders. We evaluated the relevance of Etnppl in maintaining brain lipid homeostasis by characterizing Etnppl across development and in coregulation with PEtN-relevant genes, as well as determining the impact to the brain lipidome after Etnppl loss. We found that Etnppl expression dramatically increased during a critical window of early brain development in mice and was also induced by glucocorticoids. Using a constitutive knockout of Etnppl (EtnpplKO), we did not observe robust changes in expression of PEtN-related genes. However, loss of Etnppl altered the phospholipid profile in the brain, resulting in increased total abundance of PE and in polyunsaturated fatty acids within PE and phosphatidylcholine species in the brain. Together, these data suggest that brain phospholipids are regulated by the phospholyase action of the enzyme Etnppl, which is induced by dietary fasting in astrocytes.
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DOI：
10.1073/pnas.1811013115
发表时间：
2018-11-13
影响因子：
11.1
作者：
Dutta DJ;Woo DH;Lee PR;Pajevic S;Bukalo O;Huffman WC;Wake H;Basser PJ;SheikhBahaei S;Lazarevic V;Smith JC;Fields RD
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影响因子：
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影响因子：
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DOI：
10.1016/j.plefa.2007.10.016
发表时间：
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影响因子：
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