Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans

The sterol regulatory element binding proteins (SREBPs) are transcription factors that govern cholesterol and fatty acid metabolism. Owing to their central role in hepatic lipid and lipoprotein metabolism their activity is tightly coordinated, and accordingly, dysregulation of the SREBP pathway is associated with the development of, amongst others, cardiovascular and non-alcohol fatty liver disease. Constitutive or inducible global ablation of Spring in mice is lethal, and therefore to interrogate the physiological role of SPRING in hepatic lipid metabolism we developed liver-specific Spring knockout mice (LKO).  In the liver of those mice, shotgun proteomics was assessed in n=6 (pooled together n=3 for each genotype) and injected twice in  Dionex Ultimate 3000 nano-LC system (Sunnyvale CA, USA) connected to an orbitrap Fusion™ Tribrid™ Mass Spectrometer (Thermo Scientific, Bremen, Germany) equipped with a nano-electrospray ion source operating in positive ion mode.

甾醇调节元件结合蛋白（SREBPs）是一类调控胆固醇和脂肪酸代谢的转录因子。鉴于其在肝脏脂质和脂蛋白代谢中的核心作用，其活性受到严格的协调控制。因此，SREBP通路的功能失调与心血管疾病、非酒精性脂肪性肝病等多种疾病的发生发展密切相关。由于Spring蛋白的恒定或诱导性全局敲除在小鼠中会导致致命，因此为了探究SPRING在肝脏脂质代谢中的生理作用，本研究开发了肝脏特异性Spring敲除小鼠（LKO）。在这些小鼠的肝脏中，对n=6（将每个基因型的样本合并为n=3）进行了蛋白质组学分析，并使用Dionex Ultimate 3000纳米液相色谱系统（位于美国加州桑尼维尔）进行两次注射，该系统连接至配备有纳米电喷雾离子源并采用正离子模式的orbitrap Fusion™ Tribrid™质谱仪（德国不来梅的Thermo Scientific公司）进行检测。