School of Graduate Studies, Molecular and Cell Biology Program, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
Nat Med. 2013 Jul;19(7):892-900. doi: 10.1038/nm.3200. Epub 2013 Jun 9.
Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. Overproduction of lipoproteins, a process that is dependent on microsomal triglyceride transfer protein (MTP), can contribute to hyperlipidemia. We show that microRNA-30c (miR-30c) interacts with the 3' untranslated region of MTP mRNA and induces its degradation, leading to reductions in MTP activity and in apolipoprotein B (APOB) secretion. miR-30c also reduces lipid synthesis independently of MTP. Hepatic overexpression of miR-30c reduced hyperlipidemia in Western diet-fed mice by decreasing lipid synthesis and the secretion of triglyceride-rich ApoB-containing lipoproteins and decreased atherosclerosis in Apoe(-/-) mice. Furthermore, inhibition of hepatic miR-30c by anti-miR-30c increased hyperlipidemia and atherosclerosis. Therefore, miR-30c coordinately reduces lipid biosynthesis and lipoprotein secretion, thereby regulating hepatic and plasma lipid concentrations. Raising miR-30c levels might be useful in treating hyperlipidemias and associated disorders.
高脂血症是各种心血管和代谢紊乱的一个风险因素。脂蛋白的过度产生，这一过程依赖于微粒体甘油三酯转移蛋白（MTP），可能导致高脂血症。我们发现 microRNA-30c（miR-30c）与 MTP mRNA 的 3'非翻译区相互作用，并诱导其降解，导致 MTP 活性和载脂蛋白 B（APOB）分泌减少。miR-30c 还可以独立于 MTP 减少脂质合成。肝过表达 miR-30c 通过减少脂质合成和富含甘油三酯的 ApoB 载脂蛋白的分泌来减少西方饮食喂养小鼠的高脂血症，并减少 Apoe(-/-)小鼠的动脉粥样硬化。此外，用抗 miR-30c 抑制肝 miR-30c 会增加高脂血症和动脉粥样硬化。因此，miR-30c 协调地减少脂质生物合成和脂蛋白分泌，从而调节肝和血浆脂质浓度。提高 miR-30c 水平可能有助于治疗高脂血症及其相关疾病。
