The effect of ethanolamine phosphate phosphorylase knockout on hepatic gene expression

Ethanolamine phosphate phospholyase (ETNPPL) is an enzyme that irreversibly degrades phospho-ethanolamine (p-ETN), an intermediate in the Kennedy pathway of phosphatidylethanolamine (PE) biosynthesis. PE is the second most abundant phospholipid in mammalian membranes. Disturbance of hepatic phospholipid homeostasis has been linked to the development of metabolic dysfunction-associated steatotic liver disease (MASLD). We generated whole-body Etnppl knockout mice to investigate the impact of genetic deletion of Etnppl on hepatic lipid metabolism. Female Etnppl+/+ and Etnppl-/- mice were fed either a chow diet for 20 weeks and livers were harvested for lipds, proteins, and gene expression studies. Full body Etnppl knockout (KO) and wild type (WT) female mice were fed a chow diet for 20 week. Livers were harvested, total RNA extracted, and poly-A selected mRNA was processed for paired-end sequencing. Differentially expressed genes were identified and affected metabolic pathways were identified by ontological analysis using DAVID.乙醇胺磷酸磷酸酶（Ethanolamine phosphate phospholyase, ETNPPL）是一类可不可逆降解磷酸乙醇胺（phospho-ethanolamine, p-ETN）的酶，而磷酸乙醇胺是磷脂酰乙醇胺（phosphatidylethanolamine, PE）生物合成肯尼迪途径（Kennedy pathway）中的中间代谢产物。磷脂酰乙醇胺是哺乳动物细胞膜中丰度排名第二的磷脂。肝脏磷脂稳态紊乱与代谢功能障碍相关脂肪性肝病（metabolic dysfunction-associated steatotic liver disease, MASLD）的发生发展存在关联。本研究构建了全身Etnppl基因敲除小鼠，以探究Etnppl基因遗传性缺失对肝脏脂质代谢的影响。将雌性Etnppl+/+与Etnppl-/-小鼠以基础饲料喂养20周后，收集其肝脏样本用于脂质、蛋白质及基因表达相关研究。此外，将全身Etnppl基因敲除（knockout, KO）与野生型（wild type, WT）雌性小鼠以基础饲料喂养20周，收集肝脏并提取总RNA，经聚腺苷酸选择性富集的mRNA被用于双端测序。通过DAVID数据库开展本体分析，鉴定得到差异表达基因及受影响的代谢通路。