Identification of novel transcriptional regulators of lipid metabolism.

脂质代谢的新型转录调节因子的鉴定。

• 批准号: 8148860
• 负责人: Elisabetta Mueller
• 金额: $ 55.17万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8148860
• 关键词: lipid metabolism; novel

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.

转录共激活因子 PGC-1α 在脂质代谢中发挥核心作用；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，这些分子可以充当辅助调节剂并响应代谢线索而打开/关闭其活性。 我们采用了生化方法和质谱分析，最近鉴定了一种新型 PGC-1α 结合分子，该分子能够在体外增强 PGC-1α 的转录活性。 我们目前正在进行功能获得和丧失的实验，评估这种新型辅助因子对 PGC-1α 调节的基因表达的影响，并且我们正在确定其对体内脂质 β 氧化的总体影响。