miR-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1.
miR-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1.
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miR-192-5p通过SCD-1调节非酒精性脂肪肝中的脂质合成
DOI：
10.3748/wjg.v23.i46.8140
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发表时间：
2017-12-14
影响因子：
4.3
通讯作者：
Fan JG
中科院分区：
文献类型：
--
作者：
Liu XL;Cao HX;Wang BC;Xin FZ;Zhang RN;Zhou D;Yang RX;Zhao ZH;Pan Q;Fan JG
目的评估非酒精性脂肪性肝病（NAFLD）模型中miR-192-5p的水平，并证明miR-192-5p在脂质积累中的作用。方法30只Sprague Dawley大鼠随机分为3组，分别饲喂标准日粮、高脂日粮和注射利拉鲁肽的高脂日粮。在16周结束时，测量肝脏miR-192-5p和硬脂酰辅酶a去饱和酶1 （SCD-1）水平。将MiR-192-5p模拟物和抑制剂以及SCD-1 siRNA转染到暴露于棕榈酸（PA）的Huh7细胞中。脂质积累通过油红O染色和甘油三酯测定来评估。双荧光素酶报告基因测定证实了直接相互作用。结果HFD大鼠肝脏miR-192-5p和SCD-1蛋白水平分别较对照组降低0.46倍和升高3.5倍，经利拉鲁肽注射液缓解后可逆转（P < 0.01）。暴露于PA的Huh7细胞miR-192-5p和SCD-1蛋白水平也分别下调和上调（P < 0.01）。在Huh7细胞中转染miR-192-5p模拟物和抑制剂分别可显著抑制和促进SCD-1蛋白水平（P < 0.01）。在野生型SCD-1中，miR-192-5p模拟物和miR-192-5p抑制剂分别抑制和增强荧光素酶活性（P < 0.01），而在突变型SCD-1中无明显作用。在pa处理的Huh7细胞中，过表达MiR-192-5p可显著降低脂质积累，转染SCD-1 siRNA可消除MiR-192-5p抑制剂加重的脂质沉积（P < 0.01）。结论本研究表明miR-192-5p在脂质合成中具有负调控作用，其直接调控SCD-1介导脂质合成。
AIM To evaluate the levels of miR-192-5p in non-alcoholic fatty liver disease (NAFLD) models and demonstrate the role of miR-192-5p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet (HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic miR-192-5p and stearoyl-CoA desaturase 1 (SCD-1) levels were measured. MiR-192-5p mimic and inhibitor and SCD-1 siRNA were transfected into Huh7 cells exposed to palmitic acid (PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays. RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic miR-192-5p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection (P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of miR-192-5p and SCD-1 protein levels, respectively (P < 0.01). Transfection with miR-192-5p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively (P < 0.01). Luciferase activity was suppressed and enhanced by miR-192-5p mimic and inhibitor, respectively, in wild-type SCD-1 (P < 0.01) but not in mutant SCD-1. MiR-192-5p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 siRNA transfection abrogated the lipid deposition aggravated by miR-192-5p inhibitor (P < 0.01). CONCLUSION This study demonstrates that miR-192-5p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.
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影响因子：
29.4
作者：
Lambert JE;Ramos-Roman MA;Browning JD;Parks EJ
通讯作者：
Parks EJ
影响因子：
9.8
作者：
Buzzetti, Elena;Pinzani, Massimo;Tsochatzis, Emmanuel A.
通讯作者：
Tsochatzis, Emmanuel A.
miR-192的下调通过诱导SREBF1导致肝脏脂肪变性和脂质积累：双酚A引发的非酒精性脂肪肝的新机制
DOI：
10.1016/j.bbalip.2017.05.001
发表时间：
2017-09-01
影响因子：
4.8
作者：
Lin, Yi;Ding, Dongxiao;Dong, Sijun
通讯作者：
Dong, Sijun
影响因子：
8
作者：
通讯作者：
--
影响因子：
15.9
作者：
Castoldi, Mirco;Spasic, Maja Vujic;Muckenthaler, Martina U.
通讯作者：
Muckenthaler, Martina U.