Cidea is associated with lipid droplets and insulin sensitivity in humans
Cidea is associated with lipid droplets and insulin sensitivity in humans
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DOI：
10.1073/pnas.0802063105
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发表时间：
2008-06-03
影响因子：
11.1
通讯作者：
Czech, Michael P.
中科院分区：
文献类型：
--
作者：
Puri, Vishwajeet;Ranjit, Srijana;Czech, Michael P.
在大的脂肪特异性脂滴中以甘油三酯形式储存能量是所有哺乳动物的基本需求。脂肪细胞中脂肪的有效隔离还可以防止骨骼肌和肝脏中的脂肪酸过载，这可能会损害胰岛素信号传导。在这里，我们报告说，锡德结构域的蛋白质Cidea，以前被认为是一种线粒体蛋白，共定位周围的脂滴与perilipin，脂肪分解的调节。当Cidea-GFP在前脂肪细胞或COS细胞中异位表达时，其极大地增强了脂滴大小。这些结果解释了先前的发现，该发现显示用RNAi消耗Cidea显著提高人脂肪细胞中的脂解。与围脂蛋白一样，Cidea和相关的脂滴蛋白Cidec/FSP 27由过氧化物酶体增殖物激活受体γ（PPAR γ）控制。用PPARy激动剂罗格列酮处理瘦或肥胖小鼠显著上调白色脂肪组织（WAT）中的Cidea表达，增加脂质沉积。明显的是，在网膜和皮下。来自BMI匹配的肥胖人的WAT，Cidea、Cidec/FSP 27和围脂蛋白的表达与胰岛素敏感性（HOMA-IR指数）正相关。因此，Cidea和其他脂滴蛋白定义了一种新的，高度调节的甘油三酯沉积在人WAT的途径。这些数据支持了一种模型，即该途径的失败导致异位脂质积聚、胰岛素抵抗及其相关的人类合并症。
Storage of energy as triglyceride in large adipdose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor gamma (PPAR gamma). Treatment of lean or obese mice with the PPARy agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans.