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	Activation of the farnesoid X receptor promotes triglyceride lowering by suppressingPhospholipase A2 G12B expression in hyperlipidemic mice
	Qingli Liu; Meng Yang; Renzhong Liu; Yang Lei; Xuekun Fu; Min Guan
	2015
会议名称	Keystone Symposia Conference- The Crossroads of Lipid Metabolism and Diabetes
会议地点	丹麦哥本哈根
英文摘要	Phospholipase A2 G12B (PLA2G12B) is an atypical member of secreted phospholipases. We previously demonstrated that PLA2G12B is a novel mediator of hepatic very low-density lipoproteins (VLDLs) secretion and transcriptional regulated by hepatocyte nuclear factor-4 alpha (HNF-4a). Farnesoid X receptor (FXR) plays a critical role in maintaining bile acids and triglycerides (TGs) homeostasis. Here we report that FXR regulates plasma TG level in part through PLA2G12B. Specifically, activation of FXR by chenodeoxycholic acid (CDCA) or a synthetic agonist GW4064 significantly decreased PLA2G12B expression in HepG2 cells. PLA2G12B expression was transcriptional repressed due to an FXR-mediated up-regulation of small heterodimer partner (SHP) which functionally suppresses HNF-4a activity. Using a high-fat-diet (HFD) mouse model to study the impact of FXR activation, we found that plasma TG level was reduced upon CDCA treatment. HFD-induced hepatic PLA2G12B expression was suppressed by CDCA. Concurrently, CDCA treatment lowered hepatic VLDL secretion rate with lipoprotein analysis demonstrating significant reduction in lipoprotein particle number and size. Collectively, our data demonstrate that activation of FXR promotes TG lowering, not only by decreasing de novo lipogenesis but also by reducing hepatic secretion of TG-rich VLDL particles in part through transcriptionally suppressing PLA2G12B expression.
收录类别	其他
语种	英语
内容类型	会议论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/7478]
专题	深圳先进技术研究院_医药所
作者单位	2015
推荐引用方式 GB/T 7714	Qingli Liu,Meng Yang,Renzhong Liu,et al. Activation of the farnesoid X receptor promotes triglyceride lowering by suppressingPhospholipase A2 G12B expression in hyperlipidemic mice[C]. 见:Keystone Symposia Conference- The Crossroads of Lipid Metabolism and Diabetes. 丹麦哥本哈根.

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