SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease.
SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease.
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DOI：
10.1038/srep37351
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发表时间：
2016-11-17
影响因子：
4.6
通讯作者：
Xie Q
中科院分区：
文献类型：
--
作者：
Liu Y;Yu F;Han Y;Li Q;Cao Z;Xiang X;Jiang S;Wang X;Lu J;Lai R;Wang H;Cai W;Bao S;Xie Q
非酒精性脂肪性肝病（NAFLD）的特征是肝细胞中脂质过度积聚。SENP 3在脂质代谢，特别是NAFLD中的作用尚不清楚。我们的研究结果表明，肝SENP 3上调NAFLD患者和动物模型在体内和肝细胞与游离脂肪酸（FFA）在体外加载后。在体外有/无FFA的SENP 3沉默或过表达肝细胞中测定细胞内脂质蓄积。证实了SENP 3的作用，基因沉默在体外与脂质积累的改善和脂质积累的增强的过表达相关。使用RNA-Seq体外测定NAFLD中SENP3相关基因。利用生物信息学方法，获得了11个与脂质代谢密切相关的独特基因。在体外对筛选出的3个基因（apoe、a2m和tnfrsf11b）进行了验证，结果表明apoe、a2m和tnfrsf11b在FFA刺激下受SENP 3的调控。与对照组相比，NAFLD患者肝内和循环APOE、A2M和TNFRSF11B升高。这些数据表明SENP 3通过下游基因在NAFLD的发展过程中在脂质代谢中起重要作用，这可能是NAFLD发展的有用信息。SENP3在NAFLD中的确切作用将在未来的研究中使用肝脏特异性条件性敲除小鼠进行研究。
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes. The role of SENP3 in lipid metabolism, particularly NAFLD, is unclear. Our results showed that hepatic SENP3 was up-regulated in NAFLD patients and an animal model in vivo and after loading hepatocytes with free fatty acids (FFA) in vitro. Intracellular lipid accumulation was determined in SENP3 silenced or overexpressed hepatocytes with/without FFA in vitro. Confirming a role for SENP3, gene silencing was associated in vitro with amelioration of lipid accumulation and overexpression with enhancement of lipid accumulation. SENP3 related genes in NAFLD were determined in vitro using RNA-Seq. Eleven unique genes closely associated with lipid metabolism were generated using bioinformatics. Three selected genes (apoe, a2m and tnfrsf11b) were verified in vitro, showing apoe, a2m and tnfrsf11b were regulated by SENP3 with FFA stimulation. Intrahepatic and circulating APOE, A2M and TNFRSF11B were elevated in NAFLD compared with controls. These data demonstrate the important role of SENP3 in lipid metabolism during the development of NAFLD via downstream genes, which may be useful information in the development of NAFLD. The precise role of SENP3 in NAFLD will be investigated using liver-specific conditional knockout mice in future studies.