肝脏脂肪酸结合蛋白（L-FABP）主要协调脂肪酸的新陈代谢，是肝脏脂质沉积发生的关键因素之一。目前人们对L-FABP降解的分子机制知之甚少。Derlin-1是内质网相关降解蛋白，在泛素化降解中至关重要。我们首先对过表达Derlin-1的IP产物进行质谱分析，发现Derlin-1可能参与L-FABP的特定功能。我们利用脂质沉积的细胞与动物模型，发现Derlin-1能够降低L-FABP的表达，同时二者具有相互作用，并且过表达Derlin-1可以缓解细胞脂质沉积水平。进一步发现L-FABP具有泛素化降解途径。由此我们猜想：Derlin-1可以调控L-FABP泛素化降解干预肝脏脂质沉积。本课题接下来将从细胞和动物水平，深入阐述Derlin-1能否调控L-FABP泛素化降解，进而缓解肝脏脂质沉积，并且在NAFLD病人中观察L-FABP的表达水平，为临床上寻找预防和治疗NAFLD新的靶点奠定理论基础。

Liver fatty acid binding protein (L-FABP) mainly regulates lipid metabolism and is an important factor in the development of lipid deposition in the liver. However, people have known little about the molecular mechanism of L-FABP degradation. Recent studies show that Derlin-1 plays a critical role in ubiquitin mediated protein degradation. We found Derlin-1 maybe regulate L-FABP through mass spectrometry of the IP products that compared Derlin-1 overexpression and control. We and constructed lipid-deposited cells and animal models to observe the expression of L-FABP and Derlin-1 and found that both had interaction，then we overexpressed Derlin-1 and found that the level of lipid deposition decreased. Further finding, the expression of L-FABP was affected by Derlin-1. So, we have a hypothesis that Derlin-1 can regulate ubiquitin-mediated L-FABP degradation, then intervene liver lipid deposition. Successful completion of this proposal will explore if Derlin-1 regulates the ubiquitination of L-FABP, then intervenes lipid deposition through HepG2 and Derlin-1 knockout mice and the expression level of L-FABP in NAFLD patients , which is extremely important for identifying novel potential therapeutic targets of NAFLD.