Letexier D, Peroni O, Pinteur C, Beylot M
INSERM U499, IFR 62, Faculté RTH LAENNEC, University Claude Bernard-Lyon 1, rue G Paradin, 69008 Lyon, France.
Diabetes Metab. 2005 Dec;31(6):558-66. doi: 10.1016/s1262-3636(07)70231-8.
ChREBP (Carbohydrate response element binding protein) is considered to mediate the stimulatory effect of glucose on the expression of lipogenic genes. Its activity is stimulated by glucose. Less is known on the control of its expression. This expression could be controlled by nutritional (glucose, fatty acids) and hormonal (insulin) factors. We examined the in vivo nutritional control of ChREBP expression in liver and adipose tissue of Wistar rats. Compared respectively to the fed state and to a high carbohydrate diet, ChREBP mRNA concentrations were not modified by fasting or a high fat diet in rat liver and adipose tissue. FAS and ACC1 mRNA concentrations were on the contrary decreased as expected by fasting and high fat diets and these variations of FAS and ACC1 mRNA were positively related to those of SREBP-1c mRNA and protein, but not of ChREBP mRNA. Therefore i) ChREBP expression appears poorly responsive to modifications of nutritional condition, ii) modifications of the expression of ChREBP do not seem implicated in the physiological control of lipogenesis. To investigate the possible role of ChREBP in pathological situations we measured its mRNA concentrations in the liver and adipose tissue of obese Zucker rats. ChREBP expression was increased in the liver but not the adipose tissue of obese rats compared to their lean littermates. These results support a role of ChREBP in the development of hepatic steatosis and hypertriglyceridemia but not of obesity in this experimental model.
碳水化合物反应元件结合蛋白（ChREBP）被认为介导了葡萄糖对脂肪生成基因表达的刺激作用。其活性受葡萄糖刺激。关于其表达的调控了解较少。这种表达可能受营养因素（葡萄糖、脂肪酸）和激素因素（胰岛素）控制。我们研究了Wistar大鼠肝脏和脂肪组织中ChREBP表达的体内营养调控。与进食状态和高碳水化合物饮食相比，禁食或高脂肪饮食对大鼠肝脏和脂肪组织中的ChREBP mRNA浓度没有影响。相反，禁食和高脂肪饮食使脂肪酸合酶（FAS）和乙酰辅酶A羧化酶1（ACC1）的mRNA浓度如预期那样降低，并且FAS和ACC1 mRNA的这些变化与固醇调节元件结合蛋白-1c（SREBP-1c）mRNA和蛋白的变化呈正相关，但与ChREBP mRNA的变化无关。因此，i）ChREBP表达似乎对营养状况的改变反应较弱，ii）ChREBP表达的改变似乎与脂肪生成的生理调控无关。为了研究ChREBP在病理情况下的可能作用，我们测量了肥胖Zucker大鼠肝脏和脂肪组织中的ChREBP mRNA浓度。与瘦的同窝大鼠相比，肥胖大鼠肝脏中的ChREBP表达增加，但脂肪组织中未增加。这些结果支持了在该实验模型中ChREBP在肝脂肪变性和高甘油三酯血症的发生发展中起作用，但在肥胖的发生发展中不起作用。
