Identification of novel transcriptional regulators of lipid metabolism.

转录共激活因子PGC-1α在脂类代谢中起着核心作用；尽管人们对其特定的调节功能进行了广泛的研究，但对于潜在的相互作用分子的识别还不是很清楚，这些分子可以作为辅助调节因子，根据代谢信号启动或关闭其活动。我们采用了一种生化方法，随后进行了质谱分析，最近鉴定了一种新的PGC-1α结合分子，它能够在体外增强PGC-1α的转录活性。通过获得和丧失功能的实验，我们目前正在评估这种新的辅因子对PGC-1α调控的基因表达的影响，并正在确定其在体内对脂质β氧化的整体影响。

The transcriptional coactivator PGC-1alpha plays a central role in lipid metabolism; although its specific regulatory functions have been extensively studied, not much is known about the identity of potential interacting molecules that could act as coregulators and switch on or off its activity in response to metabolic cues. We have undertaken a biochemical approach followed by mass spectrometry and recently characterized a novel PGC-1alpha binding molecule that is able to enhance PGC-1alpha's transcriptional activity in vitro. By gain-and loss-of-function experiments, we are currently assessing the effects of this novel cofactor on the expression of genes regulated by PGC-1alpha and we are determining its overall effects on lipid beta-oxidation in vivo.