D3Validation, Fondazione Istituto Italiano di Tecnologia, via Morego 30, 16163, Genova, Italy.
Scuola Superiore Sant'Anna. via Piazza Martiri della Libertà, 33, 56127, Pisa, Italy.
Sci Rep. 2018 Aug 14;8(1):12142. doi: 10.1038/s41598-018-30553-z.
Fatty acid amide hydrolase (FAAH) is an important enzyme for lipid metabolism and an interesting pharmacological target, given its role in anandamide breakdown. The FAAH genotype is the most widely used mouse model to investigate the effects of a complete pharmacological inhibition of this enzyme. In this paper, we explore, by means of label-free SWATH proteomics, the changes in protein expression occurring in the liver of FAAH knockout (KO) mice. We identified several altered biological processes and pathways, like fatty acid synthesis and glycolysis, which explain the observed phenotype of this mouse. We also observed the alteration of other proteins, like carboxylesterases and S-methyltransferases, apparently not immediately related to FAAH, but known to have important biological roles. Our study, reporting more than 3000 quantified proteins, offers an in-depth analysis of the liver proteome of this model.
脂肪酸酰胺水解酶(FAAH)是脂质代谢的重要酶,也是一个有趣的药理学靶点,因为它在分解花生四烯酸酰胺中发挥作用。FAAH 基因型是最广泛用于研究这种酶完全药理学抑制作用的小鼠模型。在本文中,我们通过无标记的 SWATH 蛋白质组学方法,研究了 FAAH 基因敲除(KO)小鼠肝脏中发生的蛋白质表达变化。我们鉴定了几个改变的生物学过程和途径,如脂肪酸合成和糖酵解,这解释了这种小鼠的表型。我们还观察到其他蛋白质的改变,如羧酸酯酶和 S-甲基转移酶,这些蛋白质显然与 FAAH 没有直接关系,但已知具有重要的生物学作用。我们的研究报告了超过 3000 种定量蛋白质,对该模型的肝脏蛋白质组进行了深入分析。