Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation
Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation
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Cideb 通过控制脂肪生成和脂肪酸氧化来调节饮食引起的肥胖、肝脏脂肪变性和胰岛素敏感性
DOI：
10.2337/db07-0040
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发表时间：
2007-10-01
期刊：
影响因子：
7.7
通讯作者：
Li, Peng
中科院分区：
文献类型：
--
作者：
Li, John Zhong;Ye, Jing;Li, Peng
目的：我们先前的研究表明，CIDA是Cide家族蛋白的一员，其序列与DNA碎片因子有同源性，并且在棕色脂肪组织中高水平表达，在肥胖的发生发展中起着重要作用。Cideb是Cide家族的另一个成员，在肝脏中高表达。我们想要了解Cideb在调节能量消耗和脂质代谢中的生理作用。研究设计和方法-我们通过同源重组产生Cideb缺失的小鼠，然后用高脂饮食(58%脂肪)喂养野生型和Cideb缺失的小鼠。然后，我们对动物的肥胖指数、食物摄入量、全身代谢率、肝脏形态、脂肪酸合成和氧化率、胰岛素敏感性和基因表达谱进行了表征。结果Cideb基因缺失的小鼠血浆甘油三酯和游离脂肪酸水平较低，对高脂饮食诱导的肥胖和活体脂肪变性具有抵抗力。此外，Cideb突变小鼠的胰岛素敏感性显著增加，全身代谢率和肝脏脂肪酸氧化率也显著增加。更重要的是，Cideb基因缺失的小鼠表现出脂肪生成减少，乙酰辅酶A羧化酶、脂肪酸合成酶和硬脂醇辅酶A去饱和酶的表达水平降低。我们进一步证明在Cideb缺陷小鼠中，甾醇反应元件结合蛋白1c的表达水平显著降低。结论Cideb是一种新的重要的肝脏脂代谢调节因子。Cideb可能成为治疗肥胖、糖尿病和肝脏脂肪变性的新靶点。
OBJECTIVE-Our previous study suggests that Cidea, a member of Cide family proteins that share sequence homology with the DNA fragmentation factor and are expressed at high levels in brown adipose tissue, plays an important role in the development of obesity. Cideb, another member of Cide family protein, is highly expressed in the liver. We would like to understand the physiological role of Cideb in the regulation of energy expenditure and lipid metabolism.RESEARCH DESIGN AND METHODS-We generated Cideb-null mice by homolog recombination and then fed both wild-type and Cideb-null mice with high-fat diet (58% fat). We then characterized the animals' adiposity index, food intake, whole-body metabolic rate, liver morphology, rate of fatty acid synthesis and oxidation, insulin sensitivity, and gene expression profile.RESULTS-Cideb-null mice had lower levels of plasma triglycerides and free fatty acids and were resistant to high-fat diet-induced obesity and live steatosis. In addition, Cideb mutant mice displayed significantly increased insulin sensitivity and enhanced rate of whole-body metabolism and hepatic fatty acid oxidation. More importantly, Cideb-null mice showed decreased lipogenesis and reduced expression levels of acetyl-CoA carboxylase, fatty acid synthase, and stearol-CoA desaturase. We further demonstrated that expression levels of sterol response element binding protein 1c was significantly decreased in Cideb-deficient mice.CONCLUSIONS-Our data demonstrate that Cideb is a novel important regulator in lipid metabolism in the liver. Cideb may represent a new therapeutic target for the treatment of obesity, diabetes, and liver steatosis.