Identification of novel transcriptional regulators of lipid metabolism.

转录辅助激活因子PGC-1α在脂类代谢中起着核心作用；尽管其特定的调节功能已被广泛研究，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，并在代谢信号反应时启动/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。我们目前正在进行获得和失去功能的实验，评估这种新的辅因子对PGC-1α调节的基因表达的影响，我们正在确定它对体内脂质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/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. We are currently performing gain-and loss-of-function experiments 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.