热卡限制对高脂饲养大鼠肝脏糖异生相关基因表达的影响

The effect of calorie restriction on the expression of liver＇s gluconeogenesis genes of rats fed a high fat diet

目的观察热卡限制对高脂饲养大鼠肝脏Forkhead转录因子O1（FoxO1）、磷酸烯醇丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G6-P）mRNA表达的影响，探讨其可能机制。方法24只雄性Wistar大鼠随机分为正常对照组（7只）、高脂组（9只）和热卡限制组（8只），分别给予正常饮食、高脂饮食和60％热卡限制饮食，共饲养12周。实验终点时取空腹血测血糖、胰岛素、甘油三酯和总胆固醇；称内脏脂肪重量及体重，计算内脏脂肪重量占体重百分比；逆转录聚合酶链法检测肝脏FoxO1、PEPCK和G—6-P mRNA表达变化；光镜观察肝脏组织学改变。结果高脂饮食大鼠出现明显腹型肥胖，空腹血糖、空腹胰岛素、甘油三酯和总胆固醇均升高，FoxO1、PEPCK和G-6-P mRNA表达较正常组分别增加18．9％、33．8％和24．6％（P值均〈0．01），且光镜下出现肝脏脂肪变性；热卡限制后大鼠体重、内脏脂肪含量显著下降，空腹血糖、空腹胰岛素、甘油三酯、总胆固醇均有所下降，FoxO1、PEPCK和G-6-P mRNA表达较正常组分别减少26．6％、35．0%和34．3％（P值均〈0．01），同时镜下脂肪变性有所好转。结论热卡限制能有效降低FoxO1、PEPCK和G-6-P基因表达，增强胰岛素信号传导，抑制肝脏糖异生，调节糖代谢。

Objective To observe the effect of calorie restriction.on the high fat diet rats＇ mRNA expressions of liver forkhead box O l（FoxOl）, phosphoenolpyruvate carboxykinase （PEPCK）, glucose-6- phosphatase （G-6-P） and to explore the possible mechanisms. Methods 24 normal 6-week-old male Wistar rats were randomly divided into three groups： normal chow group （NC, n = 7）, high fat diet group （HF, n = 9） and calorie restriction group （CR, n = 8）. They were fed for 12 weeks. At the end of the experiment, the rats were sacrificed and their fasting blood glucose （FBG）, insulin （INS）, triglycerides （TG）, total cholesterol （TC） were measured. Their visceral fat （VF） and body weight （BW） were also measured and VF/BW was calculated. Gene expression was investigated by using semi-quantitative RT-PCR methods. Liver histology was studied with HE stained slides. Results Compared with the NC group, HF group rats developed visceral obesity which was accompanied by higher FBG, plasma INS, TG, and TC. The levels of FoxO1, PEPCK, and G-6-P increased by 18.9%, 33.8%, and 24.6%, respectively （P 〈 0.01）. Liver steatosis was observed with microscopy. The BW, VF FBG, INS, TG and TC of the CR group rats were lower in comparison to those of the HF group. The levels of FoxO1, PEPCK and G-6-P were lower by 26.6%, 35.0%, 34.3% （P 〈 0.01）. Meanwhile, liver steatosis was also milder. Conclusion Calorie restriction can inhibit the expressions of FoxO1, PEPCK and G-6-P, strengthen insulin signal conduction, suppress gluconeogenesis and thus regulate glycometabolism.