Li Duan, Cheng Min, Niu Yuqiang, Chi Xiaojing, Liu Xiuying, Fan Jingjing, Fan Heng, Chang Yongsheng, Yang Wei
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100076, P.R. China;; Department of Microbiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100076, P.R. China.
Int J Biol Sci. 2017 Feb 25;13(3):349-357. doi: 10.7150/ijbs.16635. eCollection 2017.
Sterol regulatory element binding proteins (SREBPs) are master regulators of hepatic lipid homeostasis. Aberrant expression of SREBPs frequently leads to lipid metabolism dysregulation. Long non-coding RNAs (lncRNAs) have been identified with diverse biological functions, but the effects of lncRNAs on lipid metabolism are rarely reported. Here, we identified a novel human specific lncRNA, lncHR1, as a negative regulator of SREBP-1c expression. Overexpression of lncHR1 inhibited expression of SREBP-1c and fatty acid synthase (FAS) and then repressed oleic acid-induced hepatic cell triglyceride (TG) and lipid droplet (LD) accumulation. , the data of established transgenic animals showed that mice with lncHR1 expression had less hepatic expression of SREBP-1c, FAS, Acetyl-CoA carboxylase α (ACCα), and less hepatic and plasma TG after being fed a high-fat diet. Therefore, we report a novel lncRNA which can decrease lipid metabolism by repressing SREBP-1c gene expression.
固醇调节元件结合蛋白（SREBPs）是肝脏脂质稳态的主要调节因子。SREBPs的异常表达常常导致脂质代谢失调。长链非编码RNA（lncRNAs）已被证实具有多种生物学功能，但lncRNAs对脂质代谢的影响鲜有报道。在此，我们鉴定出一种新的人类特异性lncRNA，即lncHR1，它是SREBP-1c表达的负调节因子。lncHR1的过表达抑制了SREBP-1c和脂肪酸合酶（FAS）的表达，进而抑制了油酸诱导的肝细胞甘油三酯（TG）和脂滴（LD）积累。此外，已建立的转基因动物的数据表明，lncHR1表达的小鼠在高脂饮食喂养后，肝脏中SREBP-1c、FAS、乙酰辅酶A羧化酶α（ACCα）的表达较低，肝脏和血浆中的TG也较少。因此，我们报道了一种新的lncRNA，它可以通过抑制SREBP-1c基因表达来降低脂质代谢。
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