MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient (db/db) mice via down-regulating FASN.
MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient (db/db) mice via down-regulating FASN.
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MiR-30c-5p 通过下调 FASN 改善瘦素受体缺陷 (db/db) 小鼠的肝脏脂肪变性
DOI：
10.18632/oncotarget.14561
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发表时间：
2017-02-21
期刊：
影响因子：
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通讯作者：
Wen Wang D
中科院分区：
文献类型：
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作者：
Fan J;Li H;Nie X;Yin Z;Zhao Y;Chen C;Wen Wang D
全世界约有15-40%的成年人患有非酒精性脂肪肝（NAFLD）。然而，目前没有药物被许可用于治疗。在这项研究中，我们观察到瘦素受体缺陷（db/db）小鼠肝脏中miR-30 c-5 p的显著减少。值得注意的是，重组腺相关病毒（rAAV）介导的miR-30 c-5 p递送足以减弱db/db小鼠中的甘油三酯积累和肝脏脂肪变性。通过计算预测、KEGG分析和Ago 2免疫共沉淀，我们鉴定了miR-30 c-5 p直接靶向脂肪酸合成酶，脂肪酸合成酶是脂肪酸生物合成的关键酶。此外，通过siRNA下调FGFR 4减弱了NAFLD的一些关键特征，包括减少甘油三酯积累和脂质沉积。我们的研究结果揭示了miR-30 c-5 p在平衡脂肪酸生物合成中的新作用，这足以减弱db/db小鼠中的甘油三酯积累和肝脏脂肪变性。
Approximately 15–40% of the general adult population suffers from non-alcoholic fatty liver disease (NAFLD) worldwide. However, no drug is currently licensed for its treatment. In this study, we observed a significant reduction of miR-30c-5p in the liver of leptin receptor-deficient (db/db) mice. Remarkably, recombinant adeno-associated virus (rAAV)-mediated delivery of miR-30c-5p was sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice. Through computational prediction, KEGG analysis and Ago2 co-immunoprecipitation, we identified that miR-30c-5p directly targeted fatty acid synthase, a key enzyme in fatty acid biosynthesis. Moreover, down-regulation of FASN by siRNA attenuated some key features of NAFLD, including decreased triglyceride accumulate and lipid deposition. Our findings reveal a new role of miR-30c-5p in counterbalancing fatty acid biosynthesis, which is sufficient to attenuate triglyceride accumulation and hepatic steatosis in db/db mice.