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: 8939638
• 负责人: Elisabetta Mueller
• 金额: $ 49.88万
• 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/8939638
• 关键词: Adipose tissue; Binding; Biochemical; Cues; Ectopic Expression; Energy Metabolism; Gene Expression; Goals; Laboratories; Lipids; Mass Spectrum Analysis; Measures; Messenger RNA; Metabolic; Mus; Pathway interactions; Physiological; Play; Role; Transcription Coactivator; cofactor; in vitro activity; in vitro testing; in vivo; interest; lipid metabolism; loss of function; novel; oxidation; programs; promoter; research study; response; subcutaneous

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 taken 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.In addition, we have screened the PGC-1alpha promoter to identify novel transcriptional pathways that turn on PGC-1alpha expression. We are currently validating the binding of these candidate factors and assessing the effects of their activation on energy metabolism.

转录辅激活因子PGC-1 α在脂质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，但对可能作为辅调节因子并响应代谢线索而开启/关闭其活性的潜在相互作用分子的身份知之甚少。 我们已经采取了生物化学的方法，然后质谱和最近的特点是一种新的PGC-1 α结合分子，能够提高PGC-1 α的体外转录活性。 我们目前正在进行功能获得和丧失实验，评估这种新的辅因子对PGC-1 α调控的基因表达的影响，并确定其对体内脂质β-氧化的总体影响。此外，我们筛选了PGC-1 α启动子，以确定打开PGC-1 α表达的新转录途径。 我们目前正在验证这些候选因子的结合，并评估其激活对能量代谢的影响。