Pérez J X, Manzano A, Tauler A, Bartrons R
Departament de Ciències Fisiològiques Humanes i de la Nutrició, Campus de Bellvitge, Universitat de Barcelona, Spain.
Int J Obes Relat Metab Disord. 1998 Jul;22(7):667-72. doi: 10.1038/sj.ijo.0800645.
To study the mechanism that controls fructose-2,6-bisphosphate (Fru-2,6-P2) accumulation, as well as the mRNAs levels of the glycolytic/gluconeogenic regulatory enzymes in the livers of fed and starved lean (fa/-) and obese (fa/fa) Zucker rats.
Rats were fed a standard chow or deprived of food for 24 h.
Male lean (fa/-) and genetically obese (fa/fa) rats (nine weeks old).
Fru-2,6-P2 concentration, 6-phosphofructo-2-kinase (PFK-2), glucokinase (GK), pyruvate kinase (PK) activities and the mRNA levels of GK, PFK-2, L-type pyruvate kinase, fructose-1,6-bisphosphatase (FBPase-1) and phosphoenolpyruvate carboxykinase (PEPCK) were analyzed.
PFK-2/FBPase-2 mRNA decreased during starvation in both fa/- and fa/fa animals. Although PFK-2/FBPase-2 mRNA levels were similar in fed lean and obese rats, PFK-2 concentration and activity were higher in fed obese than in fed lean animals, which might explain the high concentration of Fru-2,6-P2 observed in obese animals. During starvation, PFK-2 protein concentration decreased, correlating with the enzymatic activity and Fru-2,6-P2 levels. The activities of GK and L-pyruvate kinase (L-PK) also increased in fed obese (fa/fa) rats compared with fed lean (fa/-) animals, but decreased during starvation. The mRNA levels of glycolytic enzymes in fed obese rats were similar (PFK-2) or higher than (GK, L-PK) in fed lean animals. During starvation, they decreased in lean and obese rats with one important exception, GK mRNA remained high in obese animals. The mRNA of gluconeogenic enzymes remained constant (FBPase-1) or increased (PEPCK) during fasting.
The changes observed might be explained by the hyperinsulinaemia observed in the liver of obese rats, which might lead to the stimulation of glycolysis and lipogenesis.
研究控制果糖-2,6-二磷酸（Fru-2,6-P2）积累的机制，以及进食和饥饿状态下瘦型（fa/-）和肥胖型（fa/fa） Zucker大鼠肝脏中糖酵解/糖异生调节酶的mRNA水平。
大鼠喂食标准饲料或禁食24小时。
雄性瘦型（fa/-）和遗传性肥胖型（fa/fa）大鼠（9周龄）。
分析Fru-2,6-P2浓度、6-磷酸果糖-2-激酶（PFK-2）、葡萄糖激酶（GK）、丙酮酸激酶（PK）活性以及GK、PFK-2、L型丙酮酸激酶、果糖-1,6-二磷酸酶（FBPase-1）和磷酸烯醇式丙酮酸羧激酶（PEPCK）的mRNA水平。
在fa/-和fa/fa动物饥饿期间，PFK-2/FBPase-2 mRNA均下降。尽管喂食状态下瘦型和肥胖型大鼠的PFK-2/FBPase-2 mRNA水平相似，但喂食状态下肥胖型大鼠的PFK-2浓度和活性高于瘦型大鼠，这可能解释了在肥胖型动物中观察到的Fru-2,6-P2高浓度现象。饥饿期间，PFK-2蛋白浓度下降，与酶活性和Fru-2,6-P2水平相关。与喂食的瘦型（fa/-）动物相比，喂食的肥胖型（fa/fa）大鼠中GK和L-丙酮酸激酶（L-PK）的活性也增加，但在饥饿期间下降。喂食的肥胖型大鼠中糖酵解酶的mRNA水平与喂食的瘦型动物相似（PFK-2）或更高（GK、L-PK）。饥饿期间，瘦型和肥胖型大鼠的糖酵解酶mRNA水平均下降，但有一个重要例外，肥胖型动物中GK mRNA仍保持高水平。禁食期间，糖异生酶的mRNA保持恒定（FBPase-1）或增加（PEPCK）。
观察到的变化可能由肥胖型大鼠肝脏中出现的高胰岛素血症所解释，这可能导致糖酵解和脂肪生成受到刺激。
