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: 7593716
• 负责人: Elisabetta Mueller
• 金额: $ 39.29万
• 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/7593716
• 关键词: Binding; Biochemical; Cues; Gene Expression; Goals; In Vitro; Laboratories; Lipids; Mass Spectrum Analysis; Metabolic; Physiological; Play; Role; Transcription Coactivator; cofactor; in vivo; interest; lipid metabolism; loss of function; novel; oxidation; research study; response

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.

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或关闭其活性。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。通过功能获得和功能丧失实验，我们目前正在评估这种新型辅助因子对pgc -1 α调控基因表达的影响，我们正在确定其对体内脂质β氧化的总体影响。