Creation of a genetic model of obesity in a teleost
Creation of a genetic model of obesity in a teleost
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DOI：
10.1096/fj.06-7503com
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发表时间：
2007-07-01
期刊：
影响因子：
4.8
通讯作者：
Cone, Roger D.
中科院分区：
文献类型：
--
作者：
Song, Youngsup;Cone, Roger D.
adipostat是大脑检测并维持脂肪细胞中以脂质形式储存的能量恒定水平的机制。adipostat的关键元素包括脂肪细胞衍生的激素瘦素，其与能量水平成比例地表达，并用于将此信息传达给中枢神经系统和中枢回路，中枢神经系统和中枢回路感知瘦素并对瘦素做出反应。阻断这些回路之一，即中枢黑皮质素系统，会破坏瘦素的作用，并在小鼠和人类中引起不同的肥胖综合征，其特征在于肥胖增加以及线性生长增加。我们在这里表明，转基因斑马鱼过表达内源性黑皮质素拮抗剂刺鼠相关蛋白（AgRP）也表现出肥胖，增加线性增长，脂肪细胞肥大。这些发现表明adipostat的关键元素起源于哺乳动物进化之前。此外，在斑马鱼中的转基因过表达的AgRP产生一个新的模型系统的能量稳态在一个简单的脊椎动物系统的遗传分析。
The adipostat is the mechanism by which the brain detects and maintains constant levels of energy stored in adipocytes in the form of lipids. Key elements of the adipostat include the adipocyte-derived hormone leptin that is expressed in proportion to energy levels and serves to communicate this information to the central nervous system and the central circuits, which sense and respond to leptin. Blockade of one of these circuits, the central melanocortin system, disrupts leptin action and causes a distinct obesity syndrome in mice and humans, characterized by increased adiposity as well as increased linear growth. We show here that transgenic zebrafish overexpressing the endogenous melanocortin antagonist agouti-related protein (AgRP) also exhibit obesity, increased linear growth, and adipocyte hypertrophy. These findings demonstrate that key elements of the adipostat originated before the evolution of mammals. Furthermore, transgenic overexpression of AgRP in zebrafish yields a new model system for the genetic analysis of energy homeostasis in a simple vertebrate system.