脂滴作为细胞内能量存储器，具有动态响应细胞能量代谢需求的功能。脂滴功能障碍及引起的脂代谢异常与多种代谢疾病密切相关，如脂肪肝，肝纤维化，糖尿病，肥胖等。然而目前脂滴动态调控的分子机理仍不是很清晰，尤其是SNAREs蛋白调控的脂滴融合，以及自噬调控的脂滴降解的研究尚在起步阶段。我们在前期研究中鉴定出一套新的SNARE复合物STX18-SNAP23-Sec22b，其可参与脂滴融合，并且干扰STX18的表达可诱导自噬基因ATG14在小脂滴上的聚集并促进脂滴通过自噬降解。另外我们还发现在自噬抑制的细胞中干扰STX18表达时，小体积脂滴累积变多。基于此，我们推测SNAREs通过调控脂滴的大小诱导脂滴自噬。我们将在本项目中阐明SNAREs调控脂滴融合与脂滴自噬的机制，及其对脂肪肝和肝癌的影响。本课题的完成将进一步完善脂滴动态调控的分子机制，并为脂代谢相关疾病的预防及开发靶向药物提供理论基础。

Lipid droplets (LDs) are intracellular organelles specialized for the storage of energy in the form of neutral lipids and are critically important for lipid metabolism. The dysfunction of lipid droplet can cause a lot of human disease, such as fatty liver, Hepatic fibrosis, diabetes, obesity and etc. So far the mechanisms of lipid droplets regulation are still poorly understood, especially how SNAREs regulate the lipid droplets fusion and how the lipophagy regulates the lipolysis. In our previous study, we found that STX18-SNAP23-SEC22b, assembling as SNARE complex, can promote lipid droplet biogenesis via regulation of their fusion. Besides, STX18 KD can promote the recruitment of ATG14 on small lipid droplet and induce lipophagy. Suppression of STX18 and autophagic ATG7 simultaneously, the accumulation of small lipid droplets increased. So we propose SNAREs can induce lipophagy via controlling the size of lipid droplets. We will figure out the mechanisms how SNAREs regulate the lipid droplets fusion and lipophagy to affect the fatty liver and cancer. The completeness of this study will help us to fully understood the regulation mechanism of lipid droplets, and provide new strategy to develop drugs for the correlated disease.