阻塞性睡眠呼吸暂停综合征（OSAS）与多种代谢疾病的发生相关，然而其具体分子机制尚属未知。ANGPTL8(A8)是由肝脏细胞分泌的一种细胞因子，参与血液甘油三酯的调节。我们前期结果发现，A8的一个SNP(rs2278426, R59W)，与OSAS引起的血脂代谢紊乱高度相关。R59W突变的OSAS病人血液中甘油三酯（TG）和胆固醇(TC)水平显著下降。此外细胞水平结果显示， R59W突变显著下调脂肪细胞TG和TC含量，以及脂类代谢相关基因的表达。据此我们提出假设，A8在OSAS导致的脂代谢紊乱中发挥关键作用，而R59W是其功能缺失型突变，对患者具有保护作用。我们将从分子细胞和动物模型等不同层面探索A8及R59W突变在OSAS导致的脂代谢紊乱过程中的作用及其分子机制。该研究将有助于加深对于OSAS与代谢性疾病之间关系的理解，并为临床上全新的治疗手段的研发提供理论基础和分子靶标。

Lipid metabolism abnormality is often associated with obstructive sleep apnoea syndrome (OSAS) and could contribute to cardiovascular risk in OSAS. Intermittent hypoxia could contribute to the pathogenesis of the metabolic alterations associated with obesity, a common feature of OSAS. However the underlying mechanism is unexplored. Using GWAS analysis, a functional SNP (Rs2278426, c.194C > T；R59W) of ANGPTL8 was identified to be associated with the levels of lipoprotein and cholesterols in OSAS patients. Patients who contains R59W mutations have much lower triglyceride and cholesterol in their blood. Furthermore, addition of ANGPTL8 protein but not the ANGPTL8 (R59W) mutant in the culture medium of adipocytes dramatically increased the level of triglyceride and cholesterol, as well as the expression levels of related enzymes which are required for TG and TC synthesis. Our further study tries to use adipocytes and mice model to characterize the functional role of ANGPTL8 and its R59W mutation in the lipoprotein metabolism in OSAS situation and tries to explore the molecular mechanism how R59W mutation impairs ANGPTL8’s function in regulation of lipid metabolism. Our research will give a good diagram how obstructive sleep apnoea syndrome contributes to the metabolic disorders.