The function of VASP in brown fat

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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.