增龄及高脂肪酸饮食对大鼠骨骼肌葡萄糖转运蛋白4 mRNA表达的影响

Effects of aging and high fatty acid diets on the expression of GLUT4 mRNA in skeletal muscle of rats

目的观察增龄及不同类型高脂肪酸饮食对大鼠骨骼肌葡萄糖转运蛋白4(GLUT4)mRNA表达的影响,探讨老年大鼠IR的机制。方法高饱和脂肪酸(HSF)、高不饱和脂肪酸(HUFA)饲养成年大鼠24周,观察FPG、FIns、FFA的变化;采用钳夹技术葡萄糖输注率(GIR)评价IR;RT-PCR测定骨骼肌GLUT4mRNA水平。结果 (1)12周和24周GIR比较,高饱和脂肪酸(HSF)组最低;24周时HSF、高不饱和脂肪酸(HUF)及正常对照(NC)组与0周相比较,分别下降了52.1%、51.6%和26.4%。(2)12周和24周HSF、HUF组与NC组比较,骨骼肌GLUT4mRNA表达差异有统计学意义,其表达与FFA呈负相关,与GIR呈正相关。(3)HSF、HUF组GIR与体重(BW)、TG、FFA、FPG、FIns呈负相关(r=-0.6076、-0.3562、-0.4228、-0.5419、-0.6441,P<0.01);多元回归分析显示,FFA、TG是GIR的影响因素。(4)随着周龄的增加,HSF、HUF组GLUT4mRNA表达比较,差异有统计学意义,其表达与周龄呈负相关。结论 HSF、HUFA饮食长期摄入可诱导大鼠IR,并造成其骨骼肌GLUT4mRNA的表达降低,IR可能与高脂肪酸饮食、增龄有关,但饮食结构的影响更重要。

Objective To investigate the effect of aging, different kinds of high fatty acid diets on the level of GLUT4 mRNA in skeletal muscle of rats and explore the mechanism of IR in aged rats. Methods Adult Rats were fed with high saturated fatty acid （HSFA） and high unsaturated fatty acid （HUFA） for 24 weeks. FPG, fasting blood insulin （Fins）, free fatty acid （FFA） were measured. IR was evaluated by glucose infusion rate （GIR） by clamp technique. The level of GLUT4 mRNA in skeletal muscle was measured by reverse transcription polymerase chain reaction technique （RT-PCR）. Results （1） The GIR showed significant difference between groups at both 12 and 24 weeks. GIR was the lowest in HSFA group. At the end of 24 weeks, GIR decreased by 51.6%, 52.1%, and 26.4% from baseline （week 0） in HSFA group, HUFA group and normal control group respectively. （2）The level of GLUT4 mRNA in skeletal muscle decreased significantly in both HSFA and HUFA groups compared with NC group （P 〈 0.01）, The level of GLUT4 mRNA was negatively correlated with FFA but positively correlated with GIR. （3）. GIR was negatively correlated with body weight （BW）, TG, FFA, FPG and Fins in HSFA and HUFA group （r=-0. 6076,-0. 3562,-0. 4228,-0. 5419,-0. 6441 ;P〈0.01）. Multiple stepwise regression showed that FFA and TG were risk factors for G1R. （4）The level of GLUT4 mRNA in skeletal muscle decreased significantly with aging in all groups. The level of GLUT4 mRNA in skeletal muscle was negatively correlated with weeks of age. Conclusion Long-term intake of HUFA and HSFA diets may induce IR and reduction of GLUT4 mRNA level in skeletal muscle of rats. IR may be associated with diet and age. However, diet style seems to be more important.