肝脏是体内糖脂代谢的重要器官,转录因子碳水化合物反应元件结合蛋白(ChREBP)是调节肝脏糖酵解及脂肪合成的重要转录因子。ChREBP与Max样蛋白X以异二聚体的形式调控葡萄糖利用及转化为脂肪过程中大量基因的表达。在ob/ob小鼠肝细胞特异性敲除ChREBP基因后能明显改善其脂肪肝及胰岛素抵抗。阐明ChREBP对糖脂代谢的调控机制及其生物学功能,可进一步解释葡萄糖诱导脂肪形成的过程,并有望为脂肪肝等代谢性疾病的干预治疗提供新的思路。本文对ChREBP的结构特征、调控机制、生物学功能及其与疾病的关系等最新进展进行综述。
The liver is the major site of carbohydrate metabolism and lipogenesis.Carbohydrate response element binding protein(ChREBP) is a major transcription factor mediating hepatic glycolysis and lipogenesis.The heterodimer formed by ChREBP and Mlx can regulates hepatic expression of glucose-responsive genes required for glucose utilization and de novo lipogenesis.Specific inhibition of liver ChREBP in ob/ob mice can improve hepatic steatosis and insulin resistance.Understanding the roles of ChREBP in hepatic glycolysis and lipogenesis can further explain glucose-induced lipogenesis and may cast new lights on the treatment of metabolic diseases including hepatic steatosis.In this paper we introduce the molecular structure,biological function,and regulatory mechanisms of ChREBP,as well as its relationship with metabolic diseases.