■增加肝脏中脂肪酸和甘油三酯的合成,主要由甾醇调节剂调节结合蛋白1c(SREBP1c)调节,是非酒精性脂肪性肝病(NAFLD)的主要特征之一。在本研究中,我们旨在确定SREBP1c与自噬介导的脂质液滴(LD)分解代谢在油酸(OA)诱导的脂质积累之间的关系。
■在OA施用后,在肝细胞(AML12细胞)中鉴定LD形成和SREBP1c诱导增加。通过针对SREBP1c的siRNA降低SREBP1c水平。LD的数量和大小由BODIPY确定,而通过免疫印迹和qRT-PCR鉴定蛋白质和mRNA的表达,分别。用免疫荧光确定LD-溶酶体共定位。
■在0.06mMOA浓度下测定增加的LD形成和SREBP1c水平。SREBP1c沉默减少了LD的数量,同时增加PPARα的mRNA水平。另一方面,在非OA和OA处理的细胞中SREBP1c沉默增强自噬介导的LD分解代谢。
■我们的结果提示SREBP1c缺乏在调节PPARα信号和自噬介导的LD分解代谢中对抗OA诱导的脂质积累的作用。
UNASSIGNED: Increased fatty acid and triglyceride synthesis in liver, majorly modulated by Sterol Regulator Elementing Binding Protein 1c (SREBP1c), is one of the main features of non-alcoholic fatty liver disease (NAFLD). In the present study, we aimed to identify the relation between SREBP1c and autophagy mediated lipid droplet (LD) catabolism in oleic acid (OA) induced lipid accumulation.
UNASSIGNED: Increased LD formation and SREBP1c induction were identified in hepatocytes (AML12 cells) following the OA administration. SREBP1c level was reduced through siRNA against SREBP1c. The amount and the size of LDs were determined by BODIPY, while protein and mRNA expressions were identified by immunoblotting and qRT-PCR, respectively. LD-lysosome colocalization was determined with immunofluorescence.
UNASSIGNED: Increased LD formation and SREBP1c levels were determined at 0.06 mM OA concentration. SREBP1c silencing reduced the number of LDs, while increasing mRNA levels of PPARα. On the other hand, SREBP1c silencing in non-OA and OA treated cells enhanced autophagy mediated LD catabolism.
UNASSIGNED: Our results implicate the effect of SREBP1c deficiency in modulating PPARα signaling and autophagy mediated LD catabolism against OA induced lipid accumulation.