运动和EGCG、肉碱对肥胖大鼠减肥和脂代谢及基因表达的影响
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摘要
目的：
研究运动和EGCG、肉碱对单纯性肥胖大鼠减肥和脂代谢及基因表达的作用,并探讨单纯性肥胖发生的分子学机制。
方法：
建立肥胖大鼠模型。研究8周高脂饮食对其体重、内脏脂肪系数、血清TG、TC HDL浓度、组织TG、肝脏PPARα、PGC-1α、AMPKα2、CPT1、MCAD表达水平的影响,然后随机选取肥胖造模成功大鼠30只进行减肥干预实验,将其分为肥胖对照组(F),运动组(S),运动+EGCG组(S+E),运动+肉碱组(S+L),运动+EGCG+肉碱干预组(S+E+L),除F组外,其他四组大鼠进行低强度有氧跑台训练。实验结束后测试各组大鼠的体重、内脏脂肪系数、血清TG、T、HDL浓度、组织TG水平、肝脏PPARα、PGC-1α、AMPKα2、CPT1、MCAD的基因及蛋白水平。
结果：
1.F组血清TG、TC高于正常对照组(C),HDL低于C组(P<0.05)；肝脏TG较C组高(P<0.05); PPARαmRNA及蛋白、PGC-1αmRNA、AMPK a2蛋白显著低于C组.(P<0.05)；
2.与F组比较,S组大鼠体重、血清TG低于F组(P<0.05)；S+E、S+L、S+E+L组大鼠体重、血清TG低于F组,同时低于S组(P<0.05)；S+L、S+E+L组血清TC、肝脏TG水平低于F组(P<0.05)；S+E+L组内脏脂肪系数低于F组,血清HDL水平高于F组(P<0.05)。
3.S组大鼠肝脏PPARα、PGC-1α、AMPKα2、CPT1、MCAD的基因及蛋白水平与F组无显著差异(P>0.05); S+E、S+L、S+E+L组的PPARα、PGC-1α、AMPKα2、 CPT1、MCAD的基因及/蛋白水平较F组有显著差异(P<0.05); S+E、S+L、S+E+L组的CPTlmRNA显著高于S组(P<0.05)；S+E+L组大鼠的PPARα、PGC-1α、AMPK α2、MCADmRNA显著高于S+E和/或S+L组(P<0.05)。
结论：
1.肥胖大鼠AMPKα2表达下降,PGC-1α、PPARα的表达减弱,同时PPAR α介导的下游靶基因CPT1转录和翻译活性下降；
2.运动可以减肥,EGCG、肉碱和两者联用可增强运动减肥的作用,PPARα、PGC-1α、AMPKα2、CPT1、MCAD因子改变可能是其机制之一。
Objective:Study the effect of exercise and EGCG, L-carnitine on the weight loss, lipid metabolism and gene expression in obese rats, and research the mechanism of obese rats.
Methods:Establish high-fat-diet obesity animal model in4-weeks-old male Sprague-Dawley rats. Study the effect of high-fat diet on the rats'weight, visceral fat coefficient, serum TG, TC, HDL level, the organization triglyceride level, the liver PPARα, PGC-1α, AMPKα2, CPT1, MCAD expression level. Then the50successful modeling rats were randomly divided into the obese control group(group F),the pure exercise intervention group(group S), the exercise+EGCG intervention group(group S+E), the exercise+L-carnitine intervention group(group S+L), the exercise+EGCG+L-carnitine intervention group(group S+E+L). In addition to the group F, the other four groups of rats accept low-intensity aerobic treadmill training. After7weeks, we compared the body weight, visceral fat coefficient, serum TG, TC, HDL level, organization trigiyceride level, the liver PPARa mRNA, PGC-1α mRNA, AMPK α2mRNA, CPTlmRNA, MCADmRNA and the PPAR a, PGC-1α, AMPK a2, CPT1, MCAD protein level of the five groups.
Results:(1)The serum TG, TC level of group F was significantly higher than the normal control group(group C), the HDL level of group F was significantly lower than group C(P<0.05).The liver triglyceride level in group F was higher than group C(P<0.05).The PPARα mRNA and protein expression, the PGC-1a mRNA, the AMPK a2protein expression of the group F were significantly lower than group C(P<0.05)
(2)Compared with group F, the weight and the serum TG level of group S were significantly lower than group F(P<0.05). The weight and the serum TG level of group S+E, S+L, S+E+L were significantly lower than group F and S(P<0.05). The serum TC level and the liver TG levels of group S+L, S+E+L were significantly lower than group F(P<0.05). The visceral fat coefficient of group S+E+L was significantly lower than group F, the serum HDL level of group S+E+L was significantly higher than group F(P<0.05)
(3)Compared with group F, there is no significant difference of the PPAR α,the PGC-1α,the AMPK a2, the CPT1, the MCAD mRNA and protein expression in group S. The PPARα, the PGC-1α, the AMPKα2, the CPTland the MCAD mRNA/protein expression of S+E, S+L, S+E+L were significantly higer than group F. The CPT1mRNA of group S+E, S+L, S+E+L were higher than group S. The PPAR a, the PGC-1a, the AMPK a2, the MCAD mRNA of group S+E+L were also higher than group S+E/S+L or both.
Conclusion:(1) Expression of AMPKa2decreased in obese rats, and it down-regulated PGC-1α expression, PPARα expression also decreased, while PPARα mediated downstream target gene-CPTl transcription and translation, CPT1expression declined.(2) Exercise can lose weight. The combination of EGCG or L-carnitine or both may enhance the role of exercise to lose weight. Speeding up the oxidation of fatty acid and altering the lipid metabolism related factors such as PPARα, PGC-1α, AMPKα2, CPT1.MCAD may be one of the possible mechanisms.
研究运动和EGCG、肉碱对单纯性肥胖大鼠减肥和脂代谢及基因表达的作用,并探讨单纯性肥胖发生的分子学机制。
方法：
建立肥胖大鼠模型。研究8周高脂饮食对其体重、内脏脂肪系数、血清TG、TC HDL浓度、组织TG、肝脏PPARα、PGC-1α、AMPKα2、CPT1、MCAD表达水平的影响,然后随机选取肥胖造模成功大鼠30只进行减肥干预实验,将其分为肥胖对照组(F),运动组(S),运动+EGCG组(S+E),运动+肉碱组(S+L),运动+EGCG+肉碱干预组(S+E+L),除F组外,其他四组大鼠进行低强度有氧跑台训练。实验结束后测试各组大鼠的体重、内脏脂肪系数、血清TG、T、HDL浓度、组织TG水平、肝脏PPARα、PGC-1α、AMPKα2、CPT1、MCAD的基因及蛋白水平。
结果：
1.F组血清TG、TC高于正常对照组(C),HDL低于C组(P<0.05)；肝脏TG较C组高(P<0.05); PPARαmRNA及蛋白、PGC-1αmRNA、AMPK a2蛋白显著低于C组.(P<0.05)；
2.与F组比较,S组大鼠体重、血清TG低于F组(P<0.05)；S+E、S+L、S+E+L组大鼠体重、血清TG低于F组,同时低于S组(P<0.05)；S+L、S+E+L组血清TC、肝脏TG水平低于F组(P<0.05)；S+E+L组内脏脂肪系数低于F组,血清HDL水平高于F组(P<0.05)。
3.S组大鼠肝脏PPARα、PGC-1α、AMPKα2、CPT1、MCAD的基因及蛋白水平与F组无显著差异(P>0.05); S+E、S+L、S+E+L组的PPARα、PGC-1α、AMPKα2、 CPT1、MCAD的基因及/蛋白水平较F组有显著差异(P<0.05); S+E、S+L、S+E+L组的CPTlmRNA显著高于S组(P<0.05)；S+E+L组大鼠的PPARα、PGC-1α、AMPK α2、MCADmRNA显著高于S+E和/或S+L组(P<0.05)。
结论：
1.肥胖大鼠AMPKα2表达下降,PGC-1α、PPARα的表达减弱,同时PPAR α介导的下游靶基因CPT1转录和翻译活性下降；
2.运动可以减肥,EGCG、肉碱和两者联用可增强运动减肥的作用,PPARα、PGC-1α、AMPKα2、CPT1、MCAD因子改变可能是其机制之一。
Objective:Study the effect of exercise and EGCG, L-carnitine on the weight loss, lipid metabolism and gene expression in obese rats, and research the mechanism of obese rats.
Methods:Establish high-fat-diet obesity animal model in4-weeks-old male Sprague-Dawley rats. Study the effect of high-fat diet on the rats'weight, visceral fat coefficient, serum TG, TC, HDL level, the organization triglyceride level, the liver PPARα, PGC-1α, AMPKα2, CPT1, MCAD expression level. Then the50successful modeling rats were randomly divided into the obese control group(group F),the pure exercise intervention group(group S), the exercise+EGCG intervention group(group S+E), the exercise+L-carnitine intervention group(group S+L), the exercise+EGCG+L-carnitine intervention group(group S+E+L). In addition to the group F, the other four groups of rats accept low-intensity aerobic treadmill training. After7weeks, we compared the body weight, visceral fat coefficient, serum TG, TC, HDL level, organization trigiyceride level, the liver PPARa mRNA, PGC-1α mRNA, AMPK α2mRNA, CPTlmRNA, MCADmRNA and the PPAR a, PGC-1α, AMPK a2, CPT1, MCAD protein level of the five groups.
Results:(1)The serum TG, TC level of group F was significantly higher than the normal control group(group C), the HDL level of group F was significantly lower than group C(P<0.05).The liver triglyceride level in group F was higher than group C(P<0.05).The PPARα mRNA and protein expression, the PGC-1a mRNA, the AMPK a2protein expression of the group F were significantly lower than group C(P<0.05)
(2)Compared with group F, the weight and the serum TG level of group S were significantly lower than group F(P<0.05). The weight and the serum TG level of group S+E, S+L, S+E+L were significantly lower than group F and S(P<0.05). The serum TC level and the liver TG levels of group S+L, S+E+L were significantly lower than group F(P<0.05). The visceral fat coefficient of group S+E+L was significantly lower than group F, the serum HDL level of group S+E+L was significantly higher than group F(P<0.05)
(3)Compared with group F, there is no significant difference of the PPAR α,the PGC-1α,the AMPK a2, the CPT1, the MCAD mRNA and protein expression in group S. The PPARα, the PGC-1α, the AMPKα2, the CPTland the MCAD mRNA/protein expression of S+E, S+L, S+E+L were significantly higer than group F. The CPT1mRNA of group S+E, S+L, S+E+L were higher than group S. The PPAR a, the PGC-1a, the AMPK a2, the MCAD mRNA of group S+E+L were also higher than group S+E/S+L or both.
Conclusion:(1) Expression of AMPKa2decreased in obese rats, and it down-regulated PGC-1α expression, PPARα expression also decreased, while PPARα mediated downstream target gene-CPTl transcription and translation, CPT1expression declined.(2) Exercise can lose weight. The combination of EGCG or L-carnitine or both may enhance the role of exercise to lose weight. Speeding up the oxidation of fatty acid and altering the lipid metabolism related factors such as PPARα, PGC-1α, AMPKα2, CPT1.MCAD may be one of the possible mechanisms.
引文
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