Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels
Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels
复制标题
DOI：
10.1016/j.bbrc.2012.07.038
复制
发表时间：
2012-08-10
影响因子：
3.1
通讯作者：
Zhang, Ren
中科院分区：
文献类型：
--
作者：
Zhang, Ren
代谢综合征是一种常见的疾病，包括糖耐量异常和血脂异常，构成了一个重大的公共卫生问题。患有高血脂的患者，如甘油三酯，患动脉粥样硬化性心血管疾病的风险很高。为了确定与新陈代谢相关的基因，我们对高脂饮食或禁食处理的小鼠的肝脏和脂肪进行了RNA-seq实验，并确定Gm6484(命名为Lipasin)是一个新的营养调节基因。人类LIPASIN是肝脏特异性的，而小鼠LIPASIN富含肝脏和脂肪，包括棕色和白色脂肪组织。肥胖会增加肝脏脂肪蛋白，而禁食则会减少脂肪中脂肪的表达。血管生成素样蛋白3(Angptl3)和血管生成素样蛋白4(ANGPTL4)是调节血脂的重要因子。LIPASIN与调节血脂所需的Angptl 3‘S N-末端结构域和介导脂蛋白脂肪酶结合的ANGPTL4’S N-末端片段具有同源性。腺病毒在小鼠体内过表达Lipasin可增加血清甘油三酯水平，而重组Lipasin可抑制LPL活性。因此，脂肪酶介导的甘油三酯升高的一个潜在机制是通过抑制LPL而减少甘油三酯的清除。因此，Lipasin是一种新的营养调节的肝脏浓缩因子，在脂质代谢中发挥作用。(C)2012 Elsevier Inc.保留所有权利。
The metabolic syndrome, a common disorder including glucose intolerance and dyslipidemia, poses a major public health issue. Patients with high blood lipids, such as triglycerides, are at high risk in developing atherosclerotic cardiovascular diseases. To identify genes involved in metabolism, we performed RNA-seq experiments on the liver and fat in mice treated with a high-fat diet or fasting, and identified Gm6484 (named Lipasin) as a novel nutritionally regulated gene. Human LIPASIN is liver specific, while the mouse one is enriched in the liver and fat, including both brown and white adipose tissues. Obesity increases liver Lipasin, whereas fasting reduces its expression in fat. ANGPTL3 (Angiopoietin-like 3) and ANGPTL4 are critical regulators of blood lipids. LIPASIN shares homology with ANGPTL3's N-terminal domain that is needed for lipid regulation, and with ANGPTL4's N-terminal segment that mediates lipoprotein lipase (LPL) binding. Lipasin overexpression by adenoviruses in mice increases serum triglyceride levels, and a recombinant Lipasin inhibits LPL activity. Therefore, a potential mechanism for Lipasin-mediated triglyceride elevation is through reduced triglyceride clearance by LPL inhibition. Lipasin is thus a novel nutritionally-regulated liver-enriched factor that plays a role in lipid metabolism. (c) 2012 Elsevier Inc. All rights reserved.