The function of VASP in brown fat

VASP在棕色脂肪中的作用

• 批准号: 203079884
• 负责人: Professor Dr. Alexander Pfeifer
• 金额: --
• 依托单位: Institut für Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/203079884?language=en
• 关键词: function; VASP; brown; fat

Brown adipose tissue (BAT) is a major site of for energy dissipation and plays an important role in human neonates, where it is essential for generation of non-shivering heat (i.e. thermogenesis). Although BAT content decreases after birth, recent studies using positron emission tomography indicate that adult humans also possess metabolically active BAT. BAT is rich in mitochondria and is innervated by the sympathetic nervous system. In addition, several publications demonstrated that BAT is also regulated by the nitric oxide (NO)/cGMP pathway. However, it was not clear how cGMP mediates its effects in BAT. Using brown fat cell models and knockout mice, we recently demonstrated that cGMP-dependent protein kinase I (PKGI, cGKI) is the specific cGMP effector that regulates BAT differentiation and mitochondrial biogenesis . The aim of this proposal is to elucidate the function of the vasodilator-stimulated phosphoprotein (VASP), which is a major substrate of PKGI, in BAT. VASP is a member of the Ena/VASP family that links cell membrane proteins, signal transduction pathways and the actin cytoskeleton. Our preliminary data show that VASP plays an important role in BAT and that – unexpectedly – the phenotype of VASP deficiency is different from PKGI deficiency in BAT.

棕色脂肪组织(BAT)是能量消耗的主要部位，在人类新生儿中起着重要的作用，对于产生非颤抖的热(即产热)是必不可少的。虽然蝙蝠的含量在出生后会减少，但最近使用正电子发射断层扫描的研究表明，成年人也有代谢活跃的蝙蝠。蝙蝠含有丰富的线粒体，由交感神经系统支配。此外，一些文献表明，BAT还受一氧化氮(NO)/cGMP途径的调控。然而，目前尚不清楚cGMP是如何在BAT中发挥作用的。利用棕色脂肪细胞模型和基因敲除小鼠，我们最近证实cGMP依赖的蛋白激酶I(PKGI，cGKI)是调节蝙蝠分化和线粒体生物发生的特异性cGMP效应因子。该建议的目的是阐明血管扩张剂刺激的磷酸蛋白(VASP)在BAT中的功能，它是PKGI的主要底物。Vasp是连接细胞膜蛋白、信号转导通路和肌动蛋白细胞骨架的Ena/Vasp家族成员。我们的初步数据表明，Vasp在BAT中起着重要的作用，而且出乎意料的是，Vasp缺陷的表型与BAT中PKGI缺陷的表型不同。