Identification of novel transcriptional regulators of lipid metabolism.

转录辅激活因子pgc -1 α在脂质代谢中起核心作用；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身份知之甚少，这些分子可以作为共同调节因子，并根据代谢提示打开/关闭其活性。我们采用生化方法，随后采用质谱法，最近表征了一种新的pgc - 1α结合分子，该分子能够增强pgc - 1α在体外的转录活性。我们目前正在进行功能获得和功能丧失实验，评估这种新型辅助因子对pgc -1 α调节的基因表达的影响，我们正在确定其对体内脂质β氧化的总体影响。

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.