The function of VASP in brown fat

褐色脂肪组织（BAT）是能量耗散的主要部位，在人类新生儿中起着重要作用，它是产生非寒颤热（即产热）所必需的。尽管BAT含量在出生后下降，但最近使用正电子发射断层扫描的研究表明，成年人也具有代谢活跃的BAT。BAT富含线粒体，受交感神经系统支配。此外，一些出版物表明BAT也受一氧化氮(NO)/cGMP途径的调节。然而，目前尚不清楚cGMP如何介导其在BAT中的作用。利用棕色脂肪细胞模型和敲除小鼠，我们最近证明cGMP依赖性蛋白激酶I （PKGI, cGKI）是调节BAT分化和线粒体生物发生的特异性cGMP效应物。本研究的目的是阐明VASP在BAT中的功能，VASP是PKGI的主要底物。VASP是连接细胞膜蛋白、信号转导途径和肌动蛋白细胞骨架的Ena/VASP家族成员。我们的初步数据显示VASP在BAT中起重要作用，并且出乎意料的是，VASP缺乏症的表型与BAT中的PKGI缺乏症不同。

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.