DHA具有促进脂解而降低鱼类体脂蓄积的作用。内质网是体内营养素的敏感感受器，其应激可激活UPR从而调控脂代谢。前期研究中，申请人发现DHA促进草鱼脂肪细胞脂解的同时，上调关键脂酶及UPR标志基因的表达。结合内质网应激促进鼠脂肪细胞脂解的报道，申请人提出内质网应激可能参与了DHA促草鱼脂肪细胞脂解过程的假说。本项目拟以草鱼为试验材料，采用离体原代脂肪细胞培养、激动剂与抑制剂处理、慢病毒介导的过表达与RNA干扰、免疫共沉淀等细胞分子生物学技术，结合在体饲喂，探究内质网应激在DHA促草鱼脂肪细胞脂解过程中的作用及机制，着重研究DHA诱导内质网应激情况下，cAMP/PKA信号通路参与调控脂酶ATGL、HSL及调控因子CGI58、Perilipin共同介导脂肪细胞脂解的机理。研究结果将有助于阐明DHA降低草鱼脂质蓄积的分子调控机制，为淡水鱼脂质代谢调控原理及技术研究提供参考资料和研究思路。

DHA could decrease triacylglycerol accumulation in fish. Endoplasmic reticulum stress (ER stress) induced-UPR signaling provides an essential mechanism to sense dietary fatty acids and regulate lipid metabolism. Our laboratory found that the expression levels of lipolytic enzymes and ER stress markers were significiantly increased in DHA-induced grass carp adipocytes lipolysis. Previous research has already determined the lipolysis response to ER stress in rat adipocytes. Hence, we hypothesize that lipolysis induced by DHA may be mediated by ER stress in grass carp adipocytes. In this project, grass carp, the unique carp species in China, would be applied as the experimental animal, the molecular biological and cell biological techniques, including cell culture, lentiviral-mediated overexpression and RNA interference, co-immunoprecipitation, as well as feeding experiment would be adopted to investigate whether DHA regulate lipolysis through “ER stress- cAMP/PKA” pathway to adjust the interaction among perilipin1, CGI-58, HSL and ATGL, aiming to construct the molecular regulatory network of transcriptional mechanism that regulates lipolysis by n-3 HUFA in fish. The results will give a new theoretical foundation and research approach for the study of lipid metabolism in freshwater fish.