ChREBP和Mlx在调控葡萄糖反应基因表达中的作用

近年的研究结果显示,葡萄糖能在转录水平调控糖酵解和生脂酶基因的表达,对肝糖类和脂类动态平衡起协同调控作用.其重要转录因子是糖反应元件结合蛋白（ChREBP）和Max样蛋白X(Mlx),葡萄糖通过ChREBP.Mlx异二聚体调控葡萄糖反应基因的转录.本文主要综述转录因子ChREBP和Mlx的结构与功能,调控葡萄糖反应基因表达的机制,以及影响转录因子表达的因素.     

转录因子ChREBP在葡萄糖诱导生脂中的作用

葡萄糖既是动物主要的能量来源和脂肪合成的底物,也可通过转录因子碳水化合物反应元件结合蛋白（ChREBP）调控脂肪生成。ChREBP是具有碱性螺旋-环-螺旋亮氨酸拉链（bHLH/ZIP）结构的转录因子,可激活糖酵解和脂肪生成相关基因的转录表达,在机体脂质代谢和葡萄糖稳态的调控中起重要作用。对ChREBP调控机制的认识,可为肥胖及相关代谢综合征的治疗和肉用动物体脂沉积的营养调控提供基础。本文就有关ChREBP表达、反式激活活性的调控,以及与其他调控因子的相互作用等方面的研究新进展作一综述。     

Glucose induces FGF21 mRNA expression through ChREBP activation in rat hepatocytes

Fibroblast growth factor 21 (FGF21) has beneficial effects of improving the plasma glucose and lipid profiles in diabetic rodents. Here, we investigated carbohydrate response element binding protein (ChREBP) involvement in the regulation of FGF21 mRNA expression in liver. Glucose stimulation and adenoviral overexpression of dominant active ChREBP increased FGF21 mRNA. Consistently, adenoviral expression of dominant negative Mlx inhibited glucose induction of FGF21 mRNA. Furthermore, deletion studies of mouse FGF21 gene promoter (−2000 to +65 bp) revealed a glucose responsive region between −74 and −52 bp. These findings suggest that FGF21 expression is regulated by ChREBP.